IMMUNOMODULATORY COMPOSITIONS OF MMTV ANTIGENS AND METHODS OF USING SAME

Abstract: The present invention relates to methods for inducing an immune response in a human to an MMTV antigen for treating or preventing a disease or disorder in a human caused by infection with MMTV or caused by exposure to a biological or chemical agent that reacts with an antibody directed against an MMTV antigen.

Description: IMMUNOMODULATORY COMPOSITIONS OF MMTV ANTIGENS AND METHODS OF USING SAME 1. INTRODUCTION The present invention relates to methods of administering to a human in need thereof an immunomodulatory composition comprising at least one mouse mammary tumor virus (MMTV) antigen for eliciting an immune response to such antigen. The present invention also relates to recombinant MMTV antigens encoded by MMTV nucleic acids and O immunomodulatory compositions comprising the same, as well as for methods for efficiently producing such antigens. The present invention also relates to compositions comprising antibodies directed to MMTV antigens for use in passive immunotherapy . 5 2. BACKGROUND OF THE INVENTION Breast cancer is itself diverse and the incidence of breast cancer in women varies world wide, Parkin et al . , 1992, VI IARC Scientific Publications No. 120, International n Agency for Research on Cancer. For example, circumpolar Inuit have about half the incidence as compared to Denmark, Canada and Connecticut, Miller et al . , 1996, Acta Oncologica 35:577-580. Changes in dietary cofactors or promoters has been proposed as the reason for the diversity in incidence of human breast cancer, including phytoestrogens, Wu et al . , 5 1996, Cancer Epidemiology, Biomarkers and Prevention 5:901- 906, and xenoestrogens, Davis et al . , 1995, Scientific American, Oct : 166-172. However, the evidence for high fat diets and environmental xenoestrogens for causing an increase in human breast cancer is unconvincing, Modan et al . , 1975, 0 Cancer Res. 35:3503-3506; Hunter et al . , 1996, N. Engl . J. Med. 334:356-361; Krieger et al . , 1994, J. Nat. Cancer Inst . 86:590-599. One known causative agent for breast cancer, albeit in mice, is mouse mammary tumor virus. Mouse mammary tumor virus is a type B retrovirus and induces mammary carcinomas (breast cancer) in susceptible mice by insertional c mutagenesis. The MMTV genome, similar to other retroviruses, encodes for three types of structural proteins, the non- glycosylated viral core proteins (gag) , the viral reverse transcriptase (pol) , and the glycoproteins of the viral envelope (env) . The major structural proteins are named according to their molecular weight and include glycoprotein 0 (gp)55, gp34, protein (p)28, pl8, pl4 and pl2. The 3' and 5 1 ends of the viral genome consist of repeated sequences known as the viral long terminal repeat (LTR) which is about 1300 base pairs (bp) in size. Within the 3 1 region of the LTR is an approximately 1000 bp open reading frame ( orf) whose 5 protein product, called the superantigen (SAg) , mediates a . profound effect on the host T cell population. Unlike other oncogenic retroviruses, MMTV does not carry a unique oncogene . Rather, upon infection of mammary epithelial cells, insertion of the MMTV provirus into the 0 host genome in the region of int-1 or int-2 or other yet unidentified gene(s) results in the activation of these genes through the enhancer activity of the glucocorticoid response element in the MMTV LTR. It has been demonstrated that mice free of MMTV can usually be immunized readily against MMTV antigens and are thereafter less susceptible to or completely resistant against challenge implants of MMTV-infected mammary tumor tissue, Blair, 1971, Isr. J. Med. Sci . 7:161-186; Wei et al . , 1993, Cancer Biol. 4:205-213. Efforts to demonstrate the presence of viruses in ° human breast cancer through search for viral particles, immunological cross-reactivity, or sequence homology have yielded contradictory results. Detectable MMTV env gene- related antigenic reactivity has been found in tissue sections of breast cancer, Mesa-Tejada et al . , 1978, Proc . Natl. Acad. Sci . USA 75:1529-1533; Levine et al . , 1980, Proc. Am. Assoc. Cancer Res. 21:170; Lloyd et al . , 1983, Cancer 51:654-661; breast cancer cells in culture, Litvinov and Golovkina, 1989, Acta Virologica 33:137-142; human milk, Zotter et al . , 1980, Eur. J. Cancer 16:455-467; in sera of patients, Day et al . , 1981, Proc. Natl. Acad. Sci. USA 78:2483-2487; in cyst fluid, Witkin et al . , 1981, J. Clin. Invest. 67:216-222; and in particles produced by a human breast carcinoma cell line, Keydar et al . , 1984, Proc. Natl. Acad. Sci. USA 81:4188-4192. Sequence homology to MMTV has been found in human DNA under low stringency conditions of hybridization, Callahan et al . , 1992, Proc. Natl. Acad. Sci. USA 79:5503-5507, and RNA related to MMTV has been detected in human breast cancer cells, Axel et al . , 1972, Nature 235:32-36. The presence of MMTV related sequences in lymphocytes from patients with breast cancer has been reported by Crepin et al . , 1984, Biochem. Biophys. Res. Comm. 118:324-331, as well as detection of reverse transcriptase (RT) activity in their monocytes . Al-Sumidaie et al . , 1988, Cancer Research 49:3879-3883 have reported the presence of MMTV-like sequences arranged as tandem repeats only in DNA from breast cancer cells. However, these results have been difficult to interpret in view of the relatively recent discovery of human endogenous retroviral sequences ("HERs"), Westley et al . , 1986, J. Virol. 60:743-749, Ono et al . , 1986, J. Virol. 60:589-598, Faff et al . , 1992, J. Gen. Virology 73:1087-1097, International Patent Publication WO 97/17470. Data which could be interpreted to demonstrate the presence of MMTV- related sequences could be more readily explained by exogenous human retroviral sequences, Pogo and Holland, 1997, Biological Trace Element Res. 56:131-142. Adding further confusion to the picture, env-gene related antigenicity has been detected in epitopes of human proteins, Hareuveni et al . , 1990, Int. J. Cancer 46:1134-1135. Thus, there have been many contradictory explanations for the cause of breast 5 cancer. Citation of a reference in this or any section of the specification shall not be construed that such reference is prior art to the present invention. 3. SUMMARY OF THE INVENTION 10 The methods of the present invention are directed to the administration of an immunomodulatory composition comprising at least one MMTV antigen to humans for eliciting an increase in a cellular or humoral immune response against MMTV for preventing or treating a disease or disorder in a I 5 human caused by MMTV infection. The present invention is based, in part, on the discovery that zoonotic transmission of MMTV to humans occurs and that MMTV infection can cause diseases and disorders in humans, including breast cancer and non-Hodgkins lyτnphoma . The present inventors have determined 20 that the variable incidence of breast cancer around the world correlates with the prevalence and viral load of MMTV in mice in different geographic locations. The methods of the present invention are also useful for preventing or treating a disease or disorder in a human caused by a biological or chemical agent that reacts with an antibody directed to a MMTV antigen. The immunomodulatory compositions comprise at least one MMTV antigen and a pharmaceutically acceptable carrier. In another embodiment of the invention, the composition comprises at least one antibody that is directed ° to a MMTV antigen, which composition can be used in passive immunotherapy for preventing or treating a disease or disorder in a human caused by MMTV infection or for preventing or treating a disease or disorder in a human caused by a biological or chemical agent that reacts with an antibody directed to a MMTV antigen. The present invention also provides for methods for c selecting a MMTV antigen that will elicit an immune response by determining whether a test MMTV antigen is reactive with an antibody or immune cell obtained from an individual that already exhibits an immune reaction to a MMTV antigen, i.e., an individual such as a human or mouse that has been exposed to or infected with MMTV, or determining whether the test 10 antigen is reactive with an antibody or immune cell obtained from an individual immunized with a MMTV antigen, and the use of such selected antigen in the immunomodulatory compositions of the invention. The present invention also provides for methods for 15 obtaining a peptide mimetic of a MMTV antigen by screening a library, e . g. , including but not limited to a combinatorial peptide library, a random peptide library or a phage expression library, with an antibody or immune cell obtained from an individual that already exhibits an immune reaction 20 to a MMTV antigen, or screening with an antibody or immune cell obtained from an individual immunized with a MMTV antigen, for example, a neutralizing mouse poly- or monoclonal antibody. Those positively reacting members of the library (the mimetic) can be used in the immunomodulatory compositions of the present invention. Such mimetics can 25 represent continuous or discontinuous epitopes of a MMTV antigen. 3.1 DEFINITIONS As used herein, the following terms will have the •a n meaning indicated. The term "MMTV antigen" refers to a peptide, which peptide comprises the full length native amino acid sequence, or a portion thereof, of a MMTV-encoded peptide, for example, including but not limited to the envelope peptide, reverse transcriptase, the core proteins, or the encoded superantigen. The term also refers to analogs of the c peptide, which are functionally, e . g. , antigenically, equivalent peptides, such as a peptide mimetic. Preferred analogs are those which are substantially homologous to the corresponding native amino acid sequence and comprise at least one native MMTV epitope, such as a neutralizing epitope. The term "MMTV antigen" also refers to a nucleic 0 acid molecule which encodes for a peptide, which peptide comprises the full length native amino acid sequence, or a portion thereof, of a MMTV-encoded protein. The term also refers to analogs of the nucleic acid molecule, which are functionally equivalent, e . g. , the molecule encodes a MMTV 5 peptide. Analogs can be those which are substantially homologous to the corresponding native nucleotide sequence and which encode for a peptide comprising at least one native MMTV epitope, such as a neutralizing epitope. The term "MMTV antigen" also refers to a peptide, which peptide comprises at 0 least one discontinuous epitope of MMTV, or an analog of the peptide. The term also refers to a nucleic acid molecule which encodes for a peptide, which peptide comprises at least one discontinuous epitope of MMTV, or an analog of the nucleic acid molecule. The term "discontinuous epitope" refers to an 5 epitope which comprises amino acid sequences derived from different positions in the primary amino acid sequence of the peptide but which are adjacent to each other in the three- dimensional structure of the peptide. The discontinuous epitope, also called a conformational epitope, can be encoded ° for by a nucleic acid molecule which comprises nucleic acid sequences encoding the three-dimensionally adjacent amino acid sequences. This is in contrast to a continuous epitope which is defined as an epitope in which the antigenic residues reside within a short sequence of amino acids, i.e, continuous to each other. The term "effective amount" refers to an amount of an antigen sufficient to induce a measurable immune response in the subject to which it is administered. The immune response may comprise, without limitation, induction of antigen-reactive antibody production, or induction of cellular or humoral immunity. The term "immunomodulatory composition" refers to a composition which comprises a MMTV antigen and a pharmaceutically acceptable carrier, which when administered to a subject causes a measurable change in the immune system function of the subject, e . g. , production of immunospecific antibodies, or production of antibodies that elicit a cell- mediated immune response. The term "pharmaceutically acceptable carrier" refers to a carrier medium that does not interfere with the effectiveness of the biological activity of the active ingredient, is chemically inert, and is not toxic to the patient to whom it is administered in the amount administered. The term "treating or preventing a disease or disorder caused by MMTV" means to inhibit the replication of the MMTV virus, to inhibit MMTV transmission, or to prevent MMTV from establishing itself in its host, or to ameliorate or alleviate the symptoms of a disease caused by MMTV infection, including but not limited to, breast cancer and non-Hodgkins lymphoma. The term also encompasses ameliorating or alleviating the symptoms of a disease caused by a biological or chemical agent that reacts with an antibody directed to a MMTV antigen. The treatment is considered therapeutic if there is a reduction in viral load, e . g. , number of copies of the virus in the blood, a decrease in mortality and/or morbidity. 4. BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows the nucleotide sequence of the complete proviral genome of one strain of mouse mammary tumor virus (SEQ ID N0:1) . Figure 2 shows the encoded amino acid sequence " of the gag-pol-pro polypeptide (SEQ ID NO: 2) . Figure 3 shows the encoded amino acid sequence of the gag-pro polypeptide (SEQ ID NO : 3 ) . Figure 4 shows the encoded amino acid sequence of the gag polypeptide (SEQ ID N0:4) . Figure 5 shows the encoded amino acid sequence of the env polypeptide (SEQ ID NO: 5) . Figure 6 shows the encoded amino acid sequence of the superantigen (SAg) polypeptide (SEQ ID N0:6). 5. DETAILED DESCRIPTION OF THE INVENTION The methods of the present invention are directed to the administration of an immunomodulatory composition comprising at least one MMTV antigen to humans for eliciting an increase in a cellular or humoral immune response against MMTV for preventing or treating a disease or disorder in a human caused by MMTV infection. The methods of the present invention are also useful for preventing or treating a disease or disorder in a human caused by a biological or chemical agent that reacts with an antibody directed to a MMTV antigen. The immunomodulatory compositions comprise at least one MMTV antigen and a pharmaceutically acceptable carrier. The MMTV antigen, as defined supra can be, inter alia, a peptide, peptide analog or nucleic acid molecule encoding such peptide or peptide analog. Such peptides can include the gag, pol and envelope proteins of MMTV as well as portions thereof . The present invention further relates to methods of expressing the MMTV antigen, including expression vectors and cell lines, both eukaryotic and prokaryotic as well as viral expression vectors, and the use of such c expressed antigen in the immunomodulatory compositions of the invention. In another embodiment of the invention, the composition comprises at least one antibody that is directed to a MMTV antigen, which composition can be used in passive immunotherapy for preventing or treating a disease or 0 disorder in a human caused by MMTV infection or for preventing or treating a disease or disorder in a human caused by a biological or chemical agent that reacts with an antibody directed to a MMTV antigen. The present invention also provides for methods for 5 selecting a MMTV antigen that will elicit an immune response by determining whether a test MMTV antigen is reactive with an antibody or immune cell obtained from an individual that already exhibits an immune reaction to a MMTV antigen, i.e., an individual exposed to or infected with MMTV, or by 0 determining whether the test antigen is reactive with an antibody or immune cell obtained from an individual immunized with an immunomodulatory composition of the present invention, and the use of such selected antigen in the immunomodulatory compositions of the invention. For example, the antibody can be a neutralizing mouse poly- or mono-clonal 5 antibody. The present invention also provides for methods for obtaining a peptide mimetic of a MMTV antigen by screening a library, e . g. , including but not limited to a combinatorial peptide library, a random peptide library or a phage 0 expression library, with an antibody or immune cell obtained from an individual that already exhibits an immune reaction to a MMTV antigen, or screening with an antibody or immune cell obtained from an individual immunized with an immunomodulatory composition of the present invention. For example, the antibody can be a neutralizing mouse poly- or mono-clonal antibody. Those positively reacting members of the library (the mimetic) can be used in the immunomodulatory compositions of the present invention. In an embodiment of the invention, at least one MMTV peptide that is antigenic or immunogenic is used in an immunomodulatory composition of the present invention. In another embodiment of the invention, at least one MMTV nucleotide sequence is used in an immunomodulatory composition of the present invention, which nucleotide sequence, upon expression in an appropriate host cell, produces at least one MMTV peptide that is antigenic or immunogenic. An antigenic peptide is capable of being immunospecifically bound by an antibody to the peptide. An immunogenic peptide is capable of eliciting an immune response to the peptide, e . g. , production of an antibody that immunospecifically binds the peptide or elicits a cell- mediated immune response directed against the peptide. The immunomodulatory compositions can be used in a solely preventative way for those subjects not exposed to MMTV or to the MMTV antibody-reactive biological or chemical agent, or in a therapeutic procedure after the recipient is already infected or exposed to MMTV or to the MMTV antibody- reactive biological or chemical agent, or both. The MMTV antigens of the invention also have utility in diagnostic immunoassays, passive immunotherapy, and generation of antiidiotypic antibodies. 5.1. MMTV PEPTIDES The present invention encompasses MMTV peptides and immunogenic or antigenic portions thereof, as well as analogs of such peptides or portions, and peptides having an amino acid sequence which represents at least one discontinuous epitope of MMTV and their use in the immunomodulatory compositions of the present invention. The peptides of the present invention include the following: (1) any peptide c having an amino acid sequence which is immunologically reactive with a anti-MMTV antibody; (2) any peptide having an amino acid sequence comprising the amino acid sequence as shown in any of Figures 2-6 (SEQ ID NOS:2-6) or an immunogenic or antigenic portion thereof of at least 6 contiguous amino acids; and (3) any peptide having an amino 0 acid sequence that represents a discontinuous epitope of a MMTV antigen and reacts with a MMTV peptide-reactive antibody. For example, an antigenic portion of the peptide shown in Figure 2 useful in the compositions of the present invention has an amino acid sequence selected from the group 5 consisting of about aa x to about aa y , wherein aa x denotes from about amino acid number 1 to about amino acid number 1746 of SEQ ID NO: 2 and aa y is about amino acid number x+9 of SEQ ID NO: 2; i.e., an amino acid sequence selected from the group consisting of amino acid sequences comprising from about aa 1 0 to about aa 10 , about aa 2 to about aa π , about aa 3 to about aa 12 , about aa 4 to about aa 13 , about aa 5 to about aa 14 , about aa 6 to about aa 15 , about aa 7 to about aa 16 , about aa 8 to about aa 17 , about aa 9 to about aa 18 , about aa 10 to about aa 19 , about aa n to about aa 20 , about aa 12 to about aa 21 , about aa 13 to about aa 22 , about aa 14 to about aa 23 , about aa 15 to about aa 24 , about aa 16 to 5 about aa 25 , about aa 17 to about aa 26 , about aa 18 to about aa 27 , about aa 19 to about aa 28 , about aa 20 to about aa 29 , about aa 21 to about aa 30 , about aa 22 to about aa 31 , about aa 23 to about aa 32 , about aa 24 to about aa 33 , about aa 25 to about aa 34 , about aa 2S to about aa 35 , about aa 27 to about aa 36 , about aa 28 to about aa 37 , 0 about aa 29 to about aa 38 , about aa 30 to about aa 39 , about aa 31 to about aa 40 , about aa 32 to about aa 41 , about aa 33 to about aa 42 , about aa 34 to about aa 43 , about aa 35 to about aa 44 , about aa 36 to about aa 45 , about aa 37 to about aa 46 , about aa 38 to about aa 47 , about aa 39 to about aa 48 , about aa 40 to about aa 49 , about aa 41 to about aa 50 , about aa 42 to about aa 51 , about aa 43 to about aa 52 , about aa 44 to about aa 53 , about aa 45 to about aa 54 , about aa 46 to c about aa 55 , about aa 47 to about aa 56 , about aa 48 to about aa 57 , about aa 49 to about aa 58 , about aa 50 to about aa 59 , about aa 51 to about aa 60 , about aa 52 to about aa 61 , about aa 53 to about 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1211 , about aa 1203 to about aa 1212 , about aa 1204 to about aa 1213 , about aa 1205 to about aa 1214 , about aa 1206 to about aa 1215 , about aa 1207 to about aa 1216 , about aa 1208 to about aa 1217 , about aa 1209 to about aa 1218 , about aa 1210 to about aa 1219 , about aa 1211 to about aa 1220 , about aa 1212 to about aa 1221 , about aa 1213 to about aa 1222 , about aa 1214 to about aa 1223 , about aa 1215 to about aa 1224 , about aa 1216 to about aa 1225 , about aa 1217 to about aa 1226 , about aa 1218 to about aa 1227 , about aa 1219 to about aa 1228 , about aa 1220 to about aa 1229 , about aa 1221 to about aa 1230 , about aa 1222 to about aa 1231 , about aa 1223 to about aa 1232 , about aa 1224 to about aa 1233 , about aa 1225 to about aa 1234 , about aa 1226 to about aa 1235 , about aa 1227 to about aa 1236 , about aa 1228 to about aa 1237 , about aa 1229 to about aa 1238 , about aa 1230 to about aa 1239 , about aa 1231 to about aa 1240 , about aa 1232 to about aa 1241 , about aa 1233 to about aa 1242 , about aa 1234 to about aa 1243 , about aa 1235 to about aa 1244 , about aa 1236 to about aa 1245 , about aa 1237 to about aa 1246 , about aa 1238 to about aa 1247 , about aa 1239 to about aa 1248 , about aa 1240 to about aa 1249 , about aa 1241 to about aa 1250 , about aa 1242 to about aa 1251 , about aa 1243 to about aa 1252 , about aa 1244 to about aa 1253 , about aa 1245 to about aa 1254 , about aa 1246 to about aa 1255 , about aa 1247 to about aa 1256 , about aa 1248 to about aa 1257 , about aa 1249 to about aa 1258 , about aa 1250 to about aa 1259 , about aa 1251 to about aa 1260 , about aa 1252 to about aa 1261 , about aa 1253 to about aa 1262 , about aa 1254 to about aa 1263 , about aa 1255 to about aa 1264 , about aa 1256 to about aa 1265 , about aa 1257 to about aa 1266 , about aa 1258 to about aa 1267 , about aa 1259 to about aa 1268 , about aa 1260 to about aa 1269 , about aa 1261 to about aa 1270 , about aa 1262 to about aa 1271 , about aa 1263 to about aa 1272 , about aa 1264 to about aa 1273 , about aa 1265 to about aa 1274 , about aa 1266 to about aa 1275 , about aa 1267 to about aa 1276 , about aa 1268 to about aa 1277 , about aa 1269 to about aa 1278 , about aa 1270 to about aa 1279 , about aa 1271 to about aa 1280 , about aa 1272 to about aa 1281 , about aa 1273 to about aa 1282 , about aa 1274 to about aa 1283 , about aa 1275 to about aa 1284 , about aa 1276 to about aa 1285 , about aa 1277 to about aa 1286 , about aa 1278 to about aa 1287 , about aa 1279 to about aa 1288 , about aa 1280 to about aa 1289 , about aa 1281 to about aa 1290 , about aa 1282 to about aa 1291 , about aa 1283 to about aa 1292 , about aa 1284 to about aa 1293 , about aa 12βs to about aa 1294 , about aa 1286 to about aa 1295 , about aa 1287 to about aa 1296 , about aa 1288 to about aa 1297 , about aa 1289 to about aa 1298 , about aa 1290 to about aa 1299 , about aa 1291 to about aa 1300 , about aa 1292 to about aa 1301 , about aa 1293 to about aa 1302 , about aa 1294 to about aa 1303 , about aa 1295 to about aa 1304 , about aa 1296 to about aa 1305 , about aa 1297 to about aa 1306 , about aa 1298 to about aa 1307 , about aa 1299 to about aa 1308 , about aa 1300 to about aa 1309 , about aa 1301 to about aa 1310 , about aa 1302 to about aa 1311 , about aa 1303 to about aa 1312 , about aa 1304 to about aa 1313 , about aa 1305 to about aa 1314 , about aa 1306 to about aa 1315 , about aa 1307 to about aa 1316 , about aa 1308 to about aa 1317 , about aa 1309 to about aa 1318 , about aa 1310 to about aa 1319 , about aa 1311 to about aa 1320 , about aa 1312 to about aa 1321 , about aa 1313 to. about aa 1322 , about aa 1314 to about aa 1323 , about aa 1315 to about aa 1324 , about aa 1316 to about aa 1325 , about aa 1317 to about aa 1326 , about aa 1318 to about aa 1327 , about aa 1319 to about aa 1328 , about aa 1320 to about aa 1329 , about aa 1321 to about aa 1330 , about aa 1322 to about aa 1331 , about aa 1323 to about aa 1332 , about aa 1324 to about aa 1333 , about aa 1325 to about aa 1334 , about aa 1326 to about aa 1335 , about aa 1327 to about aa 1336 , about aa 1328 to about aa 1337 , about aa 1329 to about aa 1338 , about aa 1330 to about aa 1339 , about aa 1331 to about aa 1340 , about aa 1332 to about aa 1341 , about aa 1333 to about aa 1342 , about aa 1334 to about aa 1343 , about aa 1335 to about aa 1344 , about aa 1336 to about aa 1345 , about aa 1337 to about aa 1346 , about aa 1338 to about aa 1347 , about aa 1339 to about aa 1348 , about aa 1340 to about aa 1349 , about aa 1341 to about aa 1350 , about aa 1342 to about aa 1351 , about aa i 343 to about aa 1352 , about aa 1344 to about aa 1353 , about aa 1345 to about aa 1354 , about aa 1346 to about aa 1355 , about aa 1347 to about aa 13S6 , about aa 1348 to about aa 1357 , about aa 1349 to about aa 1358 , about aa 1350 to about aa 1359 , about aa 1351 to about aa 1360 , about aa 1352 to about aa 1361 , about aa 1353 to about aa 1362 , about aa 1354 to about aa 1363 , about aa 1355 to about aa 1364 , about aa 1356 to about aa 1365 , about aa 1357 to about aa 1366 , about aa 1358 to about aa 1367 , about aa 1359 to about aa 1368 , about aa 1360 to about aa 1369 , about aa 1361 to about aa 1370 , about aa 1362 to about aa 1371 , about aa 1363 to about aa 1372 , about aa 1364 to about aa 1373 , about aa 1365 to about aa 1374 , about aa 1366 to about aa 1375 , about aa 1367 to about aa 1376 , about aa 1368 to about aa 1377 , about aa 1369 to about aa 1378 , about aa 1370 to about aa 1379 , about aa 1371 to about aa 1380 , about aa 1372 to about aa 1381 , about aa 1373 to about aa 1382 , about aa 1374 to about aa 1383 , about aa 1375 to about aa 1384 , about aa 1376 to about aa 138s , about aa 1377 to about aa 1386 , about aa 1378 to about aa 1387 , about aa 1379 to about aa 1388 , about aa 1380 to about aa 1389 , about aa 1381 to about aa 1390 , about aa 1382 to about aa 1391 , about aa 1383 to about aa 1392 , about aa 1384 to about aa 1393 , about aa 1385 to about aa 1394 , about aa 1386 to about aa 1395 , about aa 1387 to about aa 1396 , about aa 1388 to about aa 1397 , about aa 1389 to about aa 1398 , about aa 1390 to about aa 1399 , about aa 1391 to about aa 1400 , about aa 1392 to about aa 1401 , about aa 1393 to about aa 1402 , about aa 1394 to about aa 1403 , about aa 1395 to about aa 1404 , about aa 1396 to about aa 1405 , about aa 1397 to about aa 1406 , about aa 1398 to about aa 1407 , about aa 1399 to about aa 1408 , about aa 1400 to about aa 1409 , about aa 1401 to about aa 1410 , about aa 1402 to about aa 1411 , about aa 1403 to about aa 1412 , about aa 1404 to about aa 1413 , about aa 1405 to about aa 1414 , about aa 1406 to about aa 141s , about aa 1407 to about aa 1416 , about aa 1408 to about aa 1417 , about aa 1409 to about aa 1418 , about aa 1410 to about aa 1419 , about aa 1411 to about aa 1420 , about aa 1412 to about aa 1421 , about aa 1413 to about aa 1422 , about aa 1414 to about aa 1423 , about aa i 4 i 5 to about aa 1424 , about aa 1416 to about aa 1425 , about aa 1417 to about aa 1426 , about aa 1418 to about aa 1427 , about aa 1419 to about aa 1428 , about aa 1420 to about aa 1429 , about aa 1421 to about aa 1430 , about aa 1422 to about aa 1431 , about aa 1423 to about aa 1432 , about aa 1424 to about aa 1433 , about aa 1425 to about aa 1434 , about aa 1426 to about aa 1435 , about aa 1427 to about aa 1436 , about aa 1428 to about aa 1437 , about aa 1429 to about aa 1438 , about aa 1430 to about aa 1439 , about aa 1431 to about aa 1440 , about aa 1432 to about aa 1441 , about aa 1433 to about aa 1442 , about aa 1434 to about aa 1443 , about aa 1435 to about aa 1444 , about aa 1436 to about aa 1445 , about aa 1437 to about aa 1446 , about aa 1438 to about aa 1447 , about aa 1439 to about aa 1448 , about aa 1440 to about aa 1449 , about aa 1441 to about aa 1450 , about aa 1442 to about aa 1451 , about aa 1443 to about aa 1452 , about aa 1444 to about aa 1453 , about aa 1445 to about aa 1454 , about aa 1446 to about aa 1455 , about aa 1447 to about aa 1456 , about aa 1448 to about aa 14S7 , about aa 1449 to about aa 1458 , about aa 1450 to about aa 1459 , about aa 1451 to about aa 1460 , about aa 1452 to about aa 1461 , about aa 1453 to about aa 1462 , about aa 1454 to about aa 1463 , about aa 1455 to about aa 1464 , about aa 1456 to about aa 1465 , about aa 1457 to about aa 1466 , about aa 1458 to about aa 1467 , about aa 1459 to about aa 1468 , about aa 1460 to about aa 1469 , about aa 1461 to about aa 1470 , about aa 1462 to about aa 1471 , about aa 1463 to about aa 1472 , about aa 1464 to about aa 1473 , about aa 1465 to about aa 1474 , about aa 1466 to about aa 1475 , about aa 1467 to about aa 1476 , about aa 1468 to about aa 1477 , about aa 1469 to about aa 1478 , about aa 1470 to about aa 1479 , about aa 1471 to about aa 1480 , about aa 1472 to about aa 1481 , about aa 1473 to about aa 1482 , about aa 1474 to about aa 1483 , about aa 1475 to about aa 1484 , about aa 1476 to about aa 1485 , about aa 1477 to about aa 1486 , about aa 1478 to about aa 1487 , about aa 1479 to about aa 1488 , about aa 1480 to about aa 1489 , about aa 1481 to about aa 1490 , about aa 1482 to about aa 1491 , about aa 1483 to about aa 1492 , about aa 1484 to about aa 1493 , about aa 1485 to about aa 1494 , about aa 1486 to about aa 1495 , about aa 1487 to about aa 1496 , about aa 1488 to about aa 1497 , about aa 1489 to about aa 1498 , about aa 1490 to about aa 1499 , about aa 1491 to about aa 1500 , about aa 1492 to about aa 1501 , about aa 1493 to about aa 1502 , about aa 1494 to about aa 1503 , about aa 1495 to about aa 1504 , about aa 1496 to about aa 1505 , about aa 1497 to about aa 1506 , about aa 1498 to about aa 1507 , about aa 1499 to about aa 1S08 , about aa 1500 to about aa 1509 , about aa 1501 to about aa 1510 , about aa 1502 to about aa 1511 , about aa 1503 to about aa 1512 , about aa 1504 to about aa 1513 , about aa 1505 to about aa 1514 , about aa 1506 to about aa 1515 , about aa 1507 to about aa 1516 , about aa 1508 to about aa 1517 , about aa 1509 to about aa 1518 , about aa 1510 to about aa 1519 , about aa 1511 to about aa 1520 , about aa 1512 to about aa 1521 , about aa 1513 to about aa 1522 , about aa 1514 to about aa 1523 , about aa 1515 to about aa 1524 , about aa 1516 to about aa 1525 , about aa 1517 to about aa 1526 , about aa 1518 to about aa 1527 , about aa 1519 to about aa 1528 , about aa 1520 to about aa 1529 , about aa 1521 to about aa 1530 , about aa 1522 to about aa 1531 , about aa 1523 to about aa 1532 , about aa 1524 to about aa 1533 , about aa 1525 to about aa 1534 , about aa 1526 to about aa 1535 , about aa 1S27 to about aa 1536 , about aa 1528 to about aa 1537 , about aa 1529 to about aa 1538 , about aa 1530 to about aa 1539 , about aa 1531 to about aa 1540 , about aa 1532 to about aa 1541 , about aa 1533 to about aa 1542 , about aa 1534 to about aa 1543 , about aa 1535 to about aa 1544 , about aa 1536 to about aa 1545 , about aa 1537 to about aa 1546 , about aa 1538 to about aa 1547 , about aa 1539 to about aa 1548 , about aa 1540 to about aa 1549 , about aa 1541 to about aa 1550 , about aa 1542 to about aa 1551 , about aa 1543 to about aa 1552 , about aa 1544 to about aa 1553 , about aa 1S45 to about aa 1554 , about aa 1546 to about aa 1555 , about aa 1547 to about aa 1556 , about aa 1548 to about aa lsS7 , about aa 1549 to about aa 1558 , about aa 1550 to about aa 1559 , about aa 1551 to about aa 1560 , about aa 1552 to about aa ls61 , about aa 1553 to about aa 1562 , about aa 1554 to about aa 1563 , about aa 1555 to about aa 1564 , about aa 1556 to about aa 1565 , about aa 1557 to about aa 1566 , about aa 1558 to about aa 1S67 , about aa 1559 to about aa 1568 , about aa 1560 to about aa 1569 , about aa 1561 to about aa 1570 , about aa 1562 to about aa 1571 , about aa 1563 to about aa 1572 , about aa 1564 to about aa 1573 , about aa 1565 to about aa 1574 , about aa 1566 to about aa 1575 , about aa 1567 to about aa 1576 , about aa 1568 to about aa 1577 , about aa 1569 to about aa 1578 , about aa 1570 to about aa 1579 , about aa 1571 to about aa 1580 , about aa 1572 to about aa i 5 βi' about aa 1573 to about aa 1582 , about aa 1574 to about aa 1583 , about aa 1575 to about aa 1584 , about aa 1576 to about aa 1585 , about aa 1577 to about aa 1586 , about aa 1578 to about aa 1587 , about aa 1579 to about aa 1588 , about aa 1580 to about aa 1589 , about aa 1581 to about aa 1590 , about aa 1582 to about aa 1591 , about aa 1583 to about aa 1592 , about aa 1584 to about aa 1593 , about aa 1585 to about aa 1594 , about aa 1586 to about aa 1595 , about aa 1587 to about aa 1S96 , about aa 1588 to about aa 1597 , about aa 1589 to about aa 1598 , about aa ls90 to about aa 1599 , about aa 1591 to about aa 1600 , about aa 1592 to about aa 1601 , about aa 1593 to about aa 1602 , about aa 1594 to about aa 1603 , about aa 1595 to about aa 1604 , about aa 1596 to about aa 1605 , about aa 1597 to about aa 1606 , about aa 1598 to about aa 1607 , about aa 1599 to about aa 1608 , about aa 1600 to about aa 1609 , about aa 1601 to about aa 1610 , about aa 1602 to about aa 1611 , about aa 1603 to about aa 1612 , about aa 1604 to about aa 1613 , about aa 1605 to about aa 1614 , about aa 1606 to about aa 1615 , about aa 1607 to about aa 1616 , about aa 1608 to about aa 1617 , about aa 1609 to about aa 1618 , about aa 1610 to about aa 1619 , about aa 1611 to about aa 1620 , about aa 1612 to about aa 1621 , about aa 1613 to about aa 1622 , about aa 1614 to about aa 1623 , about aa 1615 to about aa 1624 , about aa 1616 to about aa 1625 , about aa 1617 to about aa 1626 , about aa 1618 to about aa 1627 , about aa 1619 to about aa 1628 , about aa 1620 to about aa 1S29 , about aa 1621 to about aa 1630 , about aa 1622 to about aa 1631 , about aa 1623 to about aa 1632 , about aa 1624 to about aa 1633 , about aa 1625 to about aa 1634 , about aa 1626 to about aa 1635 , about aa 1627 to about aa 1636 , about aa 1628 to about aa 1637 , about aa 1629 to about aa 1638 , about aa 1630 to about aa 1639 , about aa 1631 to about aa 1640 , about aa 1632 to about aa 1641 , about aa 1633 to about aa 1642 , about aa 1634 to about aa 1643 , about aa 1635 to about aa 1644 , about aa 1636 to about aa 1645 , about aa 1637 to about aa 1646 , about aa 1638 to about aa 1647 , about aa 1639 to about aa 1648 , about aa 1640 to about aa 1649 , about aa 1641 to about aa 1650 , about aa 1642 to about aa 1651 , about aa 1643 to about aa 1652 , about aa 1644 to about aa 1653 , about aa 1645 to about aa 1654 , about aa 1646 to about aa 1655 , about aa 1647 to about aa 1656 , about aa 1648 to about aa 1657 , about aa 1649 to about aa 1658 , about aa 1650 to about aa 1659 , about aa 1651 to about aa 1660 , about aa 1652 to about aa 1661 , about aa 1653 to about aa i 662 about aa 1654 to about aa 1663 , about aa 1655 to about aa 1664 , about aa 1656 to about aa 1665 , about aa 1657 to about aa 1666 , about aa 1658 to about aa 1667 , about aa 1659 to about aa 1668 , about aa 1660 to about aa 1669 , about aa 1661 to about aa 1670 , about aa 1662 to about aa 1671 , about aa 1663 to about aa 1672 , about aa 1664 to about aa 1673 , about aa 1665 to about aa 1674 , about aa 1666 to about aa 1675 , about aa i 667 to about aa 1676 , about aa 1668 to about aa 1677 , about aa 1669 to about aa 1678 , about aa 1670 to about aa 1679 , about aa 1671 to about aa 1680 , about aa 1672 to about aa 1681 , about aa 1673 to about aa 1682 , about aa 1674 to about aa 1683 , about aa 167Ξ to about aa 1684 , about aa 1676 to about aa 1685 , about aa 1677 to about aa 1686 , about aa 1678 to about aa 1687 , about aa 1679 to about aa 1688 , about aa 1680 to about aa 1689 , about aa 1681 to about aa 1690 , about aa 1682 to about aa 1691 , about aa 1683 to about aa 1692 , about aa 1684 to about aa 1693 , about aa 1685 to about aa 1694 , about aa 1686 to about aa 1695 , about aa 1687 to about aa 1696 , about aa 1688 to about aa 1697 , about aa 1689 to about aa 1698 , about aa 1690 to about aa 1699 , about aa 1691 to about aa 1700 , about aa 1692 to about aa 1701 , about aa 1693 to about aa 1702 , about aa 1694 to about aa 1703 , about aa 1695 to about aa 1704 , about aa 1696 to about aa 1705 , about aa 1697 to about aa 1706 , about aa 1698 to about aa 1707 , about aa 1699 to about aa 1708 , about aa 1700 to about aa 1709 , about aa 1701 to about aa 1710 , about aa 1702 to about aa 1711 , about aa 1703 to about aa 1712 , about aa 1704 to about aa 1713 , about aa 1705 to about aa 1714 , about aa 1706 to about aa 1715 , about aa 1707 to about aa 1716 , about aa 1708 to about aa 1717 , about aa 1709 to about aa 1718 , about aa 1710 to about aa 1719 , about aa 1711 to about aa 1720 , about aa 1712 to about aa 1721 , about aa 1713 to about aa 1722 , about aa 1714 to about aa 1723 , about aa 1715 to about aa 1724 , about aa 1716 to about aa 1725 , about aa 1717 to about aa 1726 , about aa 1718 to about aa 1727 , about aa 1719 to about aa 1728 , about aa 1720 to about aa 1729 , about aa 1721 to about aa 1730 , about aa 1722 to about aa 1731 , about aa 1723 to about aa 1732 , about aa 1724 to about aa 1733 , about aa 1725 to about aa 1734 , about aa 1726 to about aa 1735 , about aa 1727 to about aa 1736 , about aa 1728 to about aa 1737 , about aa 1729 to about aa 1738 , about aa 1730 to about aa 1739 , about aa 1731 to about aa 1740 , about aa 1732 to about aa 1741 , about aa 1733 to about aa 1742 , about aa 1734 to about aa 1743 , about aa 1735 to about aa 1744 , about aa 1736 to about aa 1745 , about aa 1737 to about aa 1746 , about aa 1738 to about aa 1747 , about aa 1739 to about aa 1748 , about aa 1740 to about aa 1749 , about aa 1741 to about aa 1750 , about aa 1742 to about aa 1751 , about aa 1743 to about aa 1752 , about aa 1744 to about aa 1753 , about aa 1745 to about aa 1754 , about aa 1746 to about aa 1755 of SEQ ID NO: 2. In yet another example, an antigenic portion of the peptide shown in Figure 2 useful in the compositions of the present invention has an amino acid sequence selected from the group consisting of about aa x to about aa y , wherein aa x denotes from about amino acid number 1 to about amino acid number 1750 of SEQ ID NO : 2 and aa y is about amino acid number x+5 of SEQ ID NO: 2; i.e., an amino acid sequence selected from the group consisting of amino acid sequences comprising 5 from about aa x to about aa 6 , about aa 2 to about aa 7 , about aa 3 to about aa 8 , about aa 4 to about aa 9 , about aa 5 to about aa 10 , and so on, through about aa 1749 to about aa 1754 , and about aa 1750 to about aa 1755 of SEQ ID NO: 2. In addition, the invention also encompasses peptide analogs that are functionally equivalent to the MMTV peptides 0 described above or encoded by the nucleic acid molecules described infra, as judged by a number of criteria, including but not limited to, the ability of the equivalent peptide to be recognized by a MMTV-reactive antibody. Such equivalent MMTV peptides may contain deletions, additions, substitutions 5 of amino acid residues within the amino acid sequence, but which result in a silent change, thus producing a functionally equivalent MMTV peptide. Amino acid substitutions can be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, o and/or amphipathic nature of the residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine and histidine; and negatively charged amino acids include aspartic acid and glutamic acid. "Functionally equivalent", as utilized herein, refers to a protein capable of being recognized by a MMTV peptide-reactive antibody. While random mutations can be made to the MMTV 0 nucleotide sequences (using random mutagenesis techniques well known to those skilled in the art) and the resulting encoded MMTV peptides tested for activity, site directed mutations of the MMTV coding sequence can be engineered (using site-directed mutagenesis techniques well known to those in the art) to generate mutant MMTV peptides with increased function, e . g. , leading to enhanced expression or antigenicity . The MMTV peptides used in the immunomodulatory compositions of the present invention are substantially pure or homogenous. A peptide sample is considered substantially pure or homogenous when at least 60 to 75% of the sample exhibits a single peptide sequence. A substantially pure peptide will preferably comprise 60 to 90% of a peptide sample, more preferably about 95% and most preferably 99%. Methods which are well known to those skilled in the art can be used to determine purity or homogeneity, such as polyacrylamide gel electrophoresis of a sample, followed by visualizing a single peptide band on a stained gel. Alternatively, resolution can be obtained using HPLC or other similar methods well known in the art. See, generally, Sambrook et al . , 1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, and Ausubel et al . (eds.), 1989, Current Protocols in Molecular Biology , Vol . I , Green Publishing Associates, Inc., and John Wiley & Sons, Inc., New York. The present invention encompasses the use of MMTV peptides which are typically purified from host cells expressing recombinant nucleotide sequences encoding the MMTV peptides in the immunomodulatory compositions. Such protein purification can be accomplished by a variety of methods well known in the art. In one embodiment, a MMTV peptide of the present invention is expressed as a fusion protein with glutathione-S-transferase. The resulting recombinant fusion protein is purified by affinity chromatography and the MMTV peptide domain is cleaved away from the heterologous moiety resulting in a substantially pure MMTV peptide sample. Other methods may be used, see for example, the techniques described in "Methods In Enzymology" , 1990, Academic Press, Inc., San Diego, "Protein Purification: Principles and practice", 1982, Springer-Verlag, New York. 5.2. MMTV NUCLEIC ACIDS The present invention also encompasses nucleic acid molecules that encode for at least one MMTV peptide or immunogenic or antigenic portion thereof, as well as an analog of such peptide or portion, and a peptide having an amino acid sequence which represents at least one discontinuous epitope of MMTV and their use in the immunomodulatory compositions of the present invention. The nucleic acid molecules of the invention include the following: (1) a nucleic acid molecule having a nucleotide sequence which comprises the nucleotide sequence depicted in Figure 1 (SEQ ID NO:l) or a portion thereof of at least 18 contiguous nucleotides; (2) any nucleic acid molecule comprising a nucleotide sequence that encodes a peptide that is immunologically reactive with an antibody directed against a MMTV peptide; (3) any nucleic acid molecule comprising a nucleotide sequence that encodes a peptide, which peptide comprises the amino acid sequence as shown in any of Figures 2-6 (SEQ ID NOS-.2-6), or a portion thereof of at least 6 contiguous amino acids; (4) any nucleic acid molecule comprising a nucleotide sequence which encodes for at least one discontinuous epitope of MMTV; (5) any nucleic acid molecule comprising a nucleotide sequence that hybridizes to the complement of the DNA sequence as shown in Figure 1 (SEQ ID NO:l) under highly stringent conditions, e . g. , hybridization to filter-bound DNA in 0.5 M NaHP0 4 , 7% sodium dodecyl sulfate (SDS) , 1 mM EDTA at 65°C, and washing in 0.1 x SSC/0.1% SDS at 68°C (Ausubel et al . , eds . , 1989, Current Protocols in Molecular Biology , Vol . I , Green Publishing Associates, Inc., and John Wiley & Sons, Inc., New York, at p. 2-10-3) and encodes a functionally equivalent MMTV peptide; (6) any nucleic acid molecule comprising a nucleotide sequence that hybridizes to the complement of the c DNA sequence as shown in Figure 1 (SEQ ID NO:l) under less stringent conditions, such as moderately stringent conditions, e . g. , washing in 0.2 x SSC/0.1% SDS at 42 °C (Ausubel et al . , 1989, supra) , yet which encodes a functionally equivalent MMTV peptide; and (7) any nucleic acid molecule comprising a nucleotide sequence that 0 hybridizes to the complement of the DNA sequence as shown in Figure 1 (SEQ ID NO:l) under less stringent conditions, such as low stringency conditions, e . g. , washing in 0.2 x SSC/ 0.1% SDS at 37°C, and encodes a functionally equivalent MMTV peptide . t For example, a nucleic acid molecule useful in the methods of the present invention has a nucleotide sequence comprising a nucleotide sequence selected from the group consisting of about nt x to about nt y of the sequence depicted in Figure 1 (SEQ ID NO:l) , wherein nt x denotes from about 0 nucleotide number 1 to about nucleotide number 8786 of SEQ ID NO:l and nt y is about nucleotide number x+17 of SEQ ID NO:l; i.e., a nucleotide sequence selected from the group consisting of nucleotide sequences comprising from about nt x to about nt 20 , about nt 2 to about nt 21 , about nt 3 to about nt 22 , about nt 4 to about nt 23 , about nt 5 to about nt 24 , and so on, 5 through about nt 8785 to about nt 8804 , and about nt 8786 to about nt 8805 of SEQ ID N0:1. In yet another example, a nucleic acid molecule useful in the methods of the present invention has a nucleotide sequence comprising a nucleotide sequence selected from the group consisting of about nt x to about nt y of the sequence depicted in Figure 1 (SEQ ID N0:1) , wherein nt x denotes from about nucleotide number 1 to about nucleotide number 8786 of SEQ ID N0:1 and nt y is about nucleotide number x+29 of SEQ ID NO : 1 ; i.e., a nucleotide sequence selected from the group consisting of nucleotide sequences comprising from about nt x to about nt 30 , about nt 2 to about nt 31 , about nt 3 c to about nt 32 , about nt 4 to about nt 33 , about nt 5 to about nt 34 , and so on, through about nt 8775 to about nt 8804 , and about nt 8776 to about nt 8805 of SEQ ID NO : 1. In addition, the invention also encompasses nucleic acid molecules that encode for MMTV peptide analogs that are functionally equivalent to the MMTV peptides described 0 herein, as judged by a number of criteria, including but not limited to, the ability of the equivalent peptide to be recognized by a MMTV-reactive antibody. Such equivalent MMTV peptides may contain deletions, additions, substitutions of amino acid residues within the amino acid sequence, but which 5 result in a silent change, thus producing a functionally equivalent MMTV peptide. Such immunologically equivalent analogs of MMTV nucleic acids can be identified by (1) making analogs of the nucleic acid molecule encoding the peptide that are truncated at the 5 ' and/or 3 ' ends of the sequence 0 and/or have one or more internal deletions; (2) expressing the analog nucleotide sequences; and (3) determining whether the resulting expressed peptide immunologically interacts with a MMTV-reactive antibody or induces the production of such antibodies in vivo. The nucleic acid molecules used in immunomodulatory 5 compositions of the present invention are substantially pure or homogenous. A nucleic acid sample is considered substantially pure or homogenous when at least 60 to 75% of the sample exhibits a single nucleotide sequence. A substantially pure nucleic acid will preferably comprise 60 to 90% of a nucleic acid sample, more preferably about 95% and most preferably 99%. Methods which are well known to those skilled in the art can be used to determine purity or homogeneity, such as polyacrylamide gel electrophoresis of a sample, followed by visualizing a single nucleic acid band on a staining gel. Higher resolution can be determined using HPLC or other similar methods well known in the art. See, c generally, Sambrook et al . , 1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, and Ausubel et al . (eds.), 1989, Current Protocols in Molecular Biology , Vol . I , Green Publishing Associates, Inc., and John Wiley & Sons, Inc., New York. 0 about The invention also encompasses (1) nucleic acid expression vectors that contain any of the foregoing nucleic acid molecules operatively associated with a regulatory element that directs expression of the nucleotide coding sequences and (2) genetically engineered host cells that 5 contain any of the foregoing nucleic acid molecules encoding a MMTV peptide operatj-vely associated with a regulatory element that directs the expression of the coding sequences in the host cell. As used herein, regulatory elements include but are not limited to, inducible and non-inducible o promoters, enhancers, operators and other elements known to those skilled in the art that drive and regulate expression. For a more detailed discussion, see Sections 5.4 and 5.5, infra . The MMTV peptides or portions thereof or discontinuous epitopes can be produced by recombinant DNA 5 technology using techniques well known in the art. Thus, methods for preparing the peptides of the invention by expressing nucleic acid molecules containing MMTV nucleotide sequences are described herein. Methods which are well known to those skilled in the art can be used to construct 0 expression vectors containing MMTV nucleotide sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vi tro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al . , 1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, and Ausubel et al . , 1989, supra . Alternatively, RNA capable of encoding a MMTV peptide, or a portion thereof, may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in "Oligonucleotide Synthesis", 1984, Gait, ed. , IRL Press, Oxford, which is incorporated by reference herein in its entirety. 5.3. SELECTING ANTIGENS FOR THE IMMUNOMODULATORY COMPOSITIONS The present invention also provides for methods for selecting or identifying candidate MMTV antigens which will provoke an immune response by determining whether the candidate antigen is reactive with antibodies or immune cells obtained from an individual exposed to or infected with MMTV or from an individual exposed to a chemical or biological agent that reacts with an antibody directed against MMTV, for example, a mouse neutralizing poly- or mono-clonal antibody. The identified or selected antigens are useful in the immunomodulatory compositions of the present invention. In one embodiment of the invention, the method is to create a peptide library of all possible peptides of a given length contained within a MMTV peptide. This library would represent a complete pepscan of the peptide. The pepscan library can then be screened with sera or immune cells obtained from an individual, for example, infected with MMTV, to determine which peptides represent an antigenic peptide, and thus, determine which peptides might be included in an immunomodulatory composition to induce an immune response in an individual. For example, the sera can be obtained from a mouse infected with MMTV. Such a complete pepscan has been described by Baughn et al . , 1996, Infection and Immunity 64:2457-2466, for the 15-kDa lipoprotein of Treponema pallidum. Overlapping decapeptides (ten amino acids) were synthesized, each of which overlapped the next by c nine amino acids and were offset by one amino acid, which allowed for a complete set of decapeptides of the protein. These were then screened with sera from syphilitic rabbits in an ELISA (enzyme-linked immunosorbent assay) to find those peptides which reacted with antibodies against syphilis. A similar approach can be used in the present invention by 0 using human sera to screen for MMTV antigens to be used in the compositions of the present invention. Another method involves combinatorial phage display libraries, including a random peptide phage display library, in which the MMTV peptide encoding nucleic acid molecules are inserted into a phage display library, expressed, and then used in a screening assay with immune sera or immune cells obtained from an individual infected with MMTV or obtained from an individual exposed to a biological or ° chemical agent that reacts with MMTV antibodies or from an individual who 0 has MMTV reactive antibodies. For example, the sera or immune cells can be obtained from a mouse infected with MMTV. Using such combinatorial phage display libraries, both continuous and discontinuous antigenic epitopes can be screened. A continuous epitope is defined as one in which the antigenic residues reside within a short sequence of 5 amino acids, i.e, continuous to each other. Discontinuous epitopes are composed of amino acid sequences derived from different positions in the primary amino acid sequence but which are adjacent in the three-dimensional structure of the protein. The discontinuous epitopes, also called ^ conformational peptides, can be encoded for by a nucleic acid molecule which comprises nucleic acid sequences encoding the three-dimensionally adjacent amino acid sequences. Such phage display peptide libraries are typically constructed in the following manner. Phages consist of DNA surrounded by coat proteins, which enable the phage to infect host bacteria and replicate themselves, producing many copies of the phage. To exploit this property, DNA sequences coding for the peptide of interest are inserted into the gene coding for a phage coat protein. As long as these insertions do not interfere with the life cycle of the phage, these modified phages will have coat proteins which display the foreign peptide. Filamentous phages are the preferred vectors, because two of their coat proteins can be easily modified to display foreign peptides, and thus foreign epitopes, on their surface. In general, these modifications are well tolerated. However, even if the modifications are not tolerated, the phage can still be rescued by a variety of techniques, including co-infection with a wild-type phage, known in the art as a helper phage . The two coat proteins of the filamentous phage of types such as M13, fd and f2 are known as pill and pVIII. There are only five copies of pill on the phage coat, while there are about 2700 copies of pVIII on the coat. However, pill can generally tolerate large insertions of up to a few hundred amino acids in length, while pVIII can tolerate only five or six amino acid insertions. As noted above, other techniques can be used to rescue phage with pVIII proteins containing larger insertions. In one embodiment of the invention, a continuous peptide library can be constructed by substantially digesting the MMTV genome, i.e., 90% or greater digestion, such that a plurality of nucleic acid fragments are obtained and inserting a fragment obtained from the digest into a phage. The nucleic acid fragments are then expressed and the phages can be screened for reactivity with immune sera or immune cells obtained, e . g. , from an individual infected with MMTV or from an individual who has an immunologic reaction to MMTV antigens. The phages which react with the immune sera or immune cells can be purified and the MMTV nucleic acid fragment or encoded peptide can be included in an c immunomodulatory composition for administration to a human. In another embodiment of the invention, a discontinuous peptide library can be constructed by substantially digesting the MMTV genome, i.e., greater than 90% digestion, such that a plurality of nucleic acid fragments are obtained, ligating the fragments to form at 0 least one ligated fragment and inserting a ligated fragment obtained from the digest into a phage. The ligated nucleic acid fragments are then expressed and the phages can be screened for reactivity with immune sera or immune cells obtained, e . g. , from an individual exposed to or infected 5 with MMTV or from an individual who has an immunologic reaction to MMTV antigens, e . g. , obtained from a mouse infected with MMTV. The phages which react with the immune sera or immune cells can be purified and the nucleic acid fragment or encoded peptide comprising the discontinuous 0 epitope can be included in an immunomodulatory composition for administration to a human. In yet another embodiment of the invention, a random peptide phage display library obtained from any source can be used to screen for MMTV epitopes. 5 5.4. EXPRESSION SYSTEMS The present invention encompasses the use of expression systems, both eukaryotic and procaryotic expression vectors, as well as viral expression vectors, which may be used to express both full-length and truncated 0 portions of MMTV peptides, as well as discontinuous epitopes identified by the methods in Section 5.3, supra . In one embodiment of the invention, the nucleotide sequence of FIG. 1 or a portion thereof, encoding a MMTV peptide is expressed in eukaryotic, procaryotic, or viral expression vectors. The nucleic acid and amino acid c sequences depicted in Figures 1-6 were obtained from GenBank, Accession No. AF033807, and depict the nucleotide and encoded amino acid sequences of one isolate of MMTV. It is envisioned that other nucleotide and amino acid sequences of other MMTV isolates can be used in the present invention. In yet another embodiment, a nucleotide sequence isolated by the 0 method described in Section 5.3, supra, is expressed in an eukaryotic, procaryotic, or viral expression vector. One embodiment of the invention encompasses the expression of MMTV peptides in a baculovirus system. Another embodiment of the invention encompasses the expression of a 5 nucleotide sequence which encodes for a discontinuous MMTV epitope in a baculovirus system. Yet another embodiment encompasses expression of a nucleotide sequence that encodes for a discontinuous MMTV epitope in a mammalian cell system. A variety of host -expression vector systems may be o utilized to express the nucleotide sequences of the present invention. Such host-expression systems represent vehicles by which the nucleotide coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequence, express a MMTV 5 peptide of the invention on the cell surface. These include, but are not limited to, microorganisms such as bacteria ( e . g. , E. coli , B . subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing MMTV nucleotide coding sequences; yeast 0 ( e . g. , Saccharomyces spp., Pichia spp . ) transformed with recombinant yeast expression vectors containing MMTV nucleotide coding sequences; insect cell systems infected with recombinant viral expression vectors ( e . g. , baculovirus) containing MMTV nucleotide coding sequences; plant cell systems infected with recombinant viral expression vectors ( e . g. , cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors ( e . g. , Ti plasmid) containing MMTV nucleotide coding sequences; and mammalian cell systems ( e. g. , COS, CHO, BHK, 293, 3T3) harboring recombinant expression constructs containing MMTV nucleotide coding sequences under the control of promoters derived from the genome of mammalian cells ( e . g. , metallothionein promoter) or from mammalian viruses ( e . g. , the adenovirus late promoter, the vaccinia virus 7.5K promoter) . In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the MMTV nucleotide sequence being expressed. For example, when a large quantity of a peptide is to be produced, for example, for the generation of pharmaceutical compositions for raising antibodies to the peptide or for inclusion of the peptide in an immunomodulatory composition, vectors which direct the expression of high levels of the peptide and allow for ready purification may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al . , 1983, EMBO J. 2:1791), in which an encoding nucleotide sequence of the present invention may be ligated individually into a vector in frame with the lacZ coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol . Chem. 264:5503-5509); and the like. pGEX vectors may also be used to express foreign peptides as fusion proteins with glutathione S-transferase (GST) . In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione . The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety. In an insect system, Autographa calif ornica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes . The virus grows in Spodoptera frugiperda cells. A MMTV gene coding sequence, e . g. , the pol protein coding sequence, may be cloned into a non-essential region (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter) . Successful insertion of a peptide coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene) . These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted gene is expressed. (E. g. , see Smith et al . , 1983, J. Virol. 46: 584; Smith, U.S. Patent No. 4,215,051). In mammalian host cells, a number of viral -based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, a MMTV nucleic acid molecule of interest may be ligated to an adenovirus transcription/translation control complex, e . g. , the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vi tro or in vivo recombination. Insertion in a non-essential region of the viral genome ( e . g. , region El or E3) will result in a recombinant virus that is viable and capable of expressing the peptide encoded by the nucleic acid molecule of interest in infected hosts. (E. g. , See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of the inserted coding sequence. These signals include the ATG initiation codon and other adjacent sequences. In cases where an entire gene, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control c signals may be needed. However, in cases where only a portion of the coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the 0 entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see 5 Bittner et al . , 1987, Methods in Enzymol . 153:516-544). Other viral expression systems can also be employed in the present invention. Such systems include, but are not limited to, vaccinia virus, recombinant viruses, or canary pox viral expression system, and the like. 0 5.5 CELL LINES The present invention encompasses the expression of MMTV peptides in animal and insect cell lines. In one embodiment of the present invention, the env glycoprotein, or a portion thereof, is expressed in a baculovirus vector in an 5 insect cell line. In another embodiment of the invention, the gag protein, or a portion thereof, is expressed in a stably transfected mammalian cell line. In yet another embodiment, a nucleic acid molecule comprising a nucleotide sequence that encodes a discontinuous epitope of MMTV is ^ expressed in a mammalian cell line. A host cell strain may be chosen which modulates the expression of the nucleic acid coding sequence, or modifies and processes the expressed peptide in a specific desired fashion. Such modifications ( e . g. , glycosylation) and processing ( e . g. cleavage) of the expressed peptide may be important for its function, e . g. , antigenicity. Different host cells have characteristics of and specific mechanisms for the post-translational processing and modification of the expressed peptides. Appropriate cell lines or host systems can be chosen to ensure the correct modification of the expressed peptide. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the expressed peptide may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3 and WI38 cell lines. For long term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the env glycoprotein, or a portion thereof, may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements ( e . g. , promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched medium, and then are switched to a selective medium. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express, for example, the MMTV env glycoprotein. A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al . , 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al . , 1980, Cell c 22:817) genes can be employed in tk " , hgprt " or aprt " cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al . , 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al . , 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance 0 to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al . , 1981, J. Mol . Biol . 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al . , 1984, Gene 30:147). 5 Alternatively, any expressed peptide may be readily purified by utilizing an antibody specific for the peptide being expressed. For example, a system described by Janknecht et al . allows for the ready purification of non- denatured fusion proteins expressed in human cell lines 0 (Janknecht, et al . , 1991, Proc. Natl. Acad. Sci. USA 88: 8972-8976) . In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus 5 are loaded onto Ni 2+ -nitriloacetic acid-agarose columns and the expressed histidine-tagged peptide is selectively eluted with imidazole-containing buffers. 5.6 IMMUNOMODULATORY COMPOSITIONS 0 AND METHODS OF ADMINISTRATION The immunomodulatory compositions of the present invention comprise an effective amount of an immunogenically active ingredient, i.e., one or more MMTV antigens, effective to produce a measurable immune response against the antigen in a subject, and a pharmaceutically acceptable carrier. The preparation of immunomodulatory compositions 5 containing an immunogenic peptide or a nucleic acid molecule encoding such peptide as the active ingredient is known to those of skill in the art. 5.6.1. DETERMINATION OF IMMUNOMODULATORY COMPOSITION 10 EFFICACY The immunopotency of the MMTV antigen can be determined by monitoring the immune response in test animals following immunization with the MMTV antigen, or by use of any immunoassay known in the art. Generation of a humoral (antibody) response and/or cell-mediated immunity, may be 15 taken as an indication of an immune response. Test animals may include mice, hamsters, dogs, cats, monkeys, rabbits, chimpanzees, etc., and human subjects. Methods of introducing the immunomodulatory composition may include oral, intracerebral , intradermal, 20 intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal or any other standard route of immunization. The immune response of the test subjects can be analyzed by various approaches such as : the reactivity of the resultant immune serum to the MMTV antigen, as assayed by known 25 techniques, e . g. , immunosorbant assay (ELISA) , immunoblots, radioimmunoprecipitations, and the like, or in the case where the MMTV antigen displays antigenicity or immunogenicity, by protection of the immunized host from infection by MMTV and/or attenuation of symptoms due to infection by MMTV in _ n the immunized host or by attenuation of symptoms due to exposure to a chemical or biological agent that cross-reacts with antibodies to a MMTV antigen. As one example of suitable animal testing of a MMTV immunomodulatory composition, a composition of the invention may be tested in mice for the ability to induce an antibody response to a MMTV antigen. BALB/c mice may be used. The c test group each receives a fixed concentration of the composition. A control group receives an injection of a buffer, e . g. , 1 mM Tris-HCl pH 9.0, without the MMTV antigen. Blood samples may be drawn from the mice every one or two weeks, and serum analyzed for antibodies to the MMTV antigen. The presence of antibodies specific for the antigen 0 may be assayed, e . g. , using an ELISA. 5.6.2. IMMUNOMODULATORY COMPOSITIONS Suitable formulations of such compositions include injectables, either as liquid solutions or suspensions; solid 5 forms suitable for solution in or suspension in liquid prior to injection may also be prepared. The compositions may also be emulsified, or the MMTV antigen encapsulated in liposomes or conjugated to polysaccharides and/or other polymers for use in a such formulation. The active immunogenic 0 ingredients are often mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredient. Suitable excipients are, for example, water saline, dextrose, glycerol , ethanol or the like, and combinations thereof. In addition, if desired, the composition may also include minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and/or adjuvants which enhance the effectiveness of the composition. Examples of adjuvants which may be effective, include, but are not limited to: mineral gels, e . g. , aluminum 0 hydroxide; surface active substances such as lysolecithin, pluronic polyols; polyanions; oil emulsions; alum; MDP; N- acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP) ; N-acetyl- nor-muramyl-L-alanyl-D-isoglutamine; and N-acetylmuramyl-L- alanyl-D-isoglutaminyl-L-alanine-2- (1 ' -2 ' -dipalmitoyl-sn- glycero-3-hydroxyphosphoryloxy) -ethylamine. The effectiveness of an adjuvant may be determined by measuring the induction of antibodies directed against MMTV antigen- containing compositions in the presence of and in the absence of various adjuvants. The MMTV antigen may be formulated into the composition as neutral or salt forms. Pharmaceutically acceptable salts include the acid addition salts (formed with free amino groups of the peptide) and which are formed with inorganic acids, such as, for example, hydrochloric or phosphoric acids, or organic acids such as acetic, oxalic, tartaric, maleic, and the like. Salts formed with free carboxyl groups may also be derived from inorganic bases, such as, for example, sodium potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine and the like. The compositions of the invention may be multivalent or univalent . Multivalent compositions can be made from recombinant viruses that direct the expression of more than one antigen. Many methods may be used to introduce the immunomodulatory compositions of the invention; these include but are not limited to oral, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal routes, and via scarification (scratching through the top layers of skin, e . g. , using a bifurcated needle) . Oral compositions can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. The compositions comprising nucleic acids of the present invention can be administered by any method known in the art for delivery of a nucleic acid to a subject, e . g. , as described herein. The patient to which an immunomodulatory composition of the present invention is administered is a mammal, preferably a human, but can also be a non-human animal including but not limited to cows, horses, sheep, pigs, fowl ( e . g. , chickens), goats, cats, dogs, hamsters, mice and rats. The patient is most preferably a human who has not been exposed to MMTV or a human who has no immunogenic reaction to MMTV antigens. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. where the composition is administered by injection, an ampoule of sterile diluent can be provided so that the ingredients may be mixed prior to administration. In a specific embodiment, a lyophilized MMTV antigen of the invention is provided in a first container; a second container comprises diluent consisting of an aqueous solution of 50% glycerin, 0.25% phenol, and an antiseptic ( e . g. , 0.005% brilliant green). The precise dose of an immunomodulatory composition to be employed will also depend on the route of administration, and the nature of the patient, and should be decided according to the judgment of the practitioner and each patient's circumstances according to standard clinical techniques. An effective immunizing amount is that amount sufficient to produce an immune response to the antigen in the host to which the composition is administered. Use of purified antigens as immunomodulatory compositions can be carried out by standard methods. For example, the purified peptide (s) should be adjusted to an appropriate concentration, formulated with any suitable adjuvant and packaged for use. In instances where the MMTV antigen is a hapten, i.e., a molecule that is antigenic in that it can react selectively with cognate antibodies, but 5 not immunogenic in that it cannot elicit an immune response, the hapten may be covalently bound to a carrier or immunogenic molecule; for instance, a large protein such as serum albumin will confer immunogenicity to the hapten coupled to it. The hapten-carrier may be formulated for use as an immunomodulatory composition. 10 Effective doses in humans of the compositions of the invention can also be extrapolated from dose-response curves derived from animal model test systems . 5.6.3. USE OF ANTIBODIES GENERATED 15 BY THE COMPOSITIONS OF THE INVENTION The antibodies generated against the antigen by administration of a MMTV antigen of the present invention also have potential uses in diagnostic immunoassays, passive immunotherapy, and generation of antiidiotypic antibodies. 20 The generated antibodies may be isolated by standard techniques known in the art ( e . g. , immunoaffinity chromatography, centrifugation, precipitation, etc.) and used in diagnostic immunoassays. The antibodies may also be used to monitor treatment and/or disease progression. Any 25 immunoassay system known in the art, such as those listed supra, may be used for this purpose including but not limited to competitive and noncompetitive assay systems using techniques such as radioimmunoassays, ELISA (enzyme-linked immunosorbent assays) , "sandwich" immunoassays, precipitin -_ reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement- fixation assays, immunoradiometric assays, fluorescent immunoassays, protein A immunoassays and immunoelectrophoresis assays, to name but a few. The immunomodulatory compositions of the present invention can also be used to produce antibodies for use in c passive immunotherapy, in which short-term protection of a host is achieved by the administration of a pre- formed antibody directed against an MMTV antigen. The antibodies generated by the immunomodulatory compositions of the present invention can also be used in the production of antiidiotypic antibody. The antiidiotypic 0 antibody can then in turn be used for immunization, in order to produce a subpopulation of antibodies that bind the initial antigen of the pathogenic microorganism or agent (Jerne, 1974, Ann. Immunol. (Paris) 125c:373; Jerne, et al . , 1982, EMBO J. 1:234) . 5 5.6.4 PACKAGING The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may, o for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Associated with such pack or dispenser device (s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. Compositions comprising an antigen of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labelled ^ for treatment of an indicated condition. The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the amended claims. Various references are cited herein, the disclosures of which are incorporated by reference in their entireties .

Claims: WHAT IS CLAIMED IS: 1. A method for inducing an immune response to MMTV in a human subject comprising administering to the c subject an immunomodulatory composition comprising a pharmaceutical carrier and at least one MMTV antigen in an amount sufficient to elicit an increase in a MMTV specific cellular or humoral response. 2. The method according to claim 1, in which the 0 .. . antigen is the MMTV env peptide or a portion thereof. 3. The method according to claim 2, in which the portion comprises at least 6 contiguous amino acids of the MMTV env peptide. 5 4. The method according to claim 1, in which the antigen is a MMTV core peptide or portion thereof. 5. The method according to claim 4, in which the o portion comprises at least 6 contiguous amino acids of a MMTV core peptide. 6. The method according to claim 1, in which the antigen is the MMTV pol peptide or portion thereof. 5 7. The method according to claim 6, in which the portion comprises at least 6 contiguous amino acids of the MMTV pol peptide. 8. The method according to claim 1, in which the 0 antigen is a nucleic acid molecule which encodes for at least one MMTV antigen. 9. The method according to claim 8, in which the nucleic acid encodes for the MMTV env peptide or a portion thereof . c 10. The method according to claim 9, in which the portion encodes at least 6 contiguous amino acids of the MMTV env peptide. 11. The method according to claim 8, in which the nucleic acid encodes for a MMTV core peptide or portion ° t,hereof . 12. The method according to claim 11, in which the portion encodes at least 6 contiguous amino acids of a MMTV core peptide. 5 13. The method according to claim 8, in which the nucleic acid encodes for the MMTV pol peptide or portion thereof . 0 14- The method according to claim 13, in which the portion encodes at least 6 contiguous amino acids of a MMTV core peptide. 15. The method according to claim 8 in which the nucleic acid encodes for a discontinuous epitope of MMTV. 5 16. The method according to claim 1 in which the human subject has not been exposed to or infected with MMTV prior to administration of the immunomodulatory composition. 0 17. The method according to claim 1 in which the human subject has no immune reactivity to a MMTV antigen prior to administration of the immunomodulatory composition. 18. The method according to claim 1, in which the immunomodulatory composition is administered by a route selected from the group consisting of an oral route, an intranasal route, an intradermal route, an intravenous route, c an intraperitoneal route and a subcutaneous route. 19. A discontinuous epitope of MMTV produced by a method comprising (a) substantially digesting the genome of MMTV to produce a plurality of MMTV nucleic acid fragments; (b) ligating the fragments to produce at least one ligated 0 nucleic acid fragment which encodes at least one peptide; (c) expressing the ligated fragment in an expression system such that the encoded peptide is expressed; (d) screening the expressed peptide with sera comprising antibodies or immune cells reactive with at least one MMTV antigen; and (e) 5 purifying the expressed peptide that positively reacts with the antibodies or immune cell . 20. A method for inducing an immune response to MMTV in a human subject comprising administering to the 0 subject an immunomodulatory composition comprising a pharmaceutically acceptable carrier and a discontinuous epitope of MMTV produced by a method comprising (a) substantially digesting the genome of MMTV to produce a plurality of MMTV nucleic acid fragments; (b) ligating the fragments to produce at least one ligated nucleic acid 5 fragment which encodes at least one peptide; (c) expressing the ligated fragment in an expression system such that the encoded peptide is expressed; (d) screening the expressed peptide with sera comprising antibodies or immune cells reactive with at least one MMTV antigen; and (e) purifying 0 the expressed peptide that positively reacts with the antibodies or immune cell, in an amount sufficient to elicit an increase in a MMTV specific cellular or humoral response.

Inventors: GERSHONI JONATHAN, STEWART THOMAS H M, GERSHONI, JONATHAN, STEWART, THOMAS, H., M.
Applicants: GERSHONI JONATHAN, INT BIOIMMUNE SYSTEMS INC, STEWART THOMAS H M, GERSHONI, JONATHAN, INTERNATIONAL BIOIMMUNE SYSTEMS, INC., STEWART, THOMAS, H., M.
Application year: 1999
Main classification: A61K39
IPC codes: A61K39, A61K48, A61P35, C07K14