METHODS FOR DIAGNOSIS AND TREATING CANCERS, AND METHODS FOR IDENTIFYING PATHOGENIC MARKERS IN A SAMPLE OF NORMAL CELLS

Abstract: The invention involves the recognition of a previously identified protein, SCP-1, as a marker for cell transformation. Diagnostic and therapeutic uses of this protein and related molecules are taught. Also disclosed is a method for identifying substances which are immunoreactive and indicative of pathological conditions, using normal cells as source material.

Description: METHODS FOR DIAGNOSIS AND TREATING CANCERS, AND METHODS FOR IDENTIFYING PATHOGENIC MARKERS IN A SAMPLE OF NORMAL CELLS RELATED APPLICATIONS This application is a continuation in part of Serial No. 08/892,702, filed July 15, 1997, incorporated by reference herein. FIELD OF THE INVENTION The invention relates to the identification of a molecule or a marker for transformed cells, such as cancer cells. It also relates to a method for identifying molecules associated with pathological conditions, such as cancer. BACKGROUND AND PRIOR ART It is fairly well established that many pathological conditions, such as infections, cancer, autoimmune disorders, etc., are characterized by the inappropriate expression of certain molecules. These molecules thus serve as "markers" for a particular pathological or abnormal condition. Apart from their use as diagnostic "targets", i.e., materials to be identified to diagnose these abnormal conditions, the molecules serve as reagents which can be used to generate diagnostic and/or therapeutic agents. A by no means limiting example of this is the use of cancer markers to produce antibodies specific to a particular marker. Yet another non-limiting example is the use of a peptide which complexes with an MHC molecule, to generate cytolytic T cells against abnormal cells. Preparation of such materials, of course, presupposes a source of the reagents used to generate these. Purification from cells is one laborious, far from sure method of doing so. Another preferred method is the isolation of nucleic acid molecules which encode a particular marker, followed by the use of the isolated encoding nucleic acid molecule to express the desired protein molecule. To date, two strategies have been employed for the detection of such antigens, in e.g., human tumors. These will be referred to as the genetic approach and the biochemical approach. The genetic approach is exemplified by, e.g., dePlaen et al., Proc. Natl. Sci. USA 85: 2275 (1988), incorporated by reference. In this approach, several hundred pools of plasmids of a cDNA library obtained from a tumor are transfected into recipient cells, such as COS cells, or into antigen-negative variants of tumor cell lines. Transfectants are screened for the expression of tumor antigens via their ability to provoke reactions by anti-tumor cytolytic T cell clones. The biochemical approach, exemplified by, e.g., Mandelboim, et al., Nature 369: 69 (1994) incorporated by reference, is based on acidic elution of peptides which have bound to MHC-class I molecules of tumor cells, followed by reversed-phase high performance liquid chromatography (HPLC). Antigenic peptides are identified after they bind to empty MHC-class I molecules of mutant cell lines, defective in antigen processing, and induce specific reactions with cytotoxic T- lymphocytes. These reactions include induction of cytolytic T cell lines (CTLs) proliferation tumor necrosis factor (TNF) release, and lysis of target cells, measurable in an MTT assay, or a 5i Cr release assay. These two approaches to the molecular definition of antigens have the following disadvantages: first, they are enormously cumbersome, time-consuming and expensive; second, they depend on the establishment of CTLs with predefined specificity; and third, their relevance in vivo for the course of the pathology of disease in question has not been proven, as the respective CTLs can be obtained not only from patients with the respective disease, but also from healthy individuals, depending on their T cell repertoire. The problems inherent to the two known approaches for the identification and molecular definition of antigens is best demonstrated by the fact that both methods have, so far, succeeded in defining only very few new antigens in human tumors. See, e.g., van der Bruggen et al., Science 254: 1643-1647 (1991); Richard et al., J. Exp. Med. 178: 489- 495 (1993); Coulie, et al., J. Exp. Med. 180: 35-42 (1994); Kawakami, et al., Proc. Natl. Acad. Sci. USA 91: 3515-3519 (1994). Further, the methodologies supra described rely on the availability of established, permanent cell lines of the cancer type under consideration. It is very difficult to establish cell lines from certain cancer types, as is shown by, e.g., Oettgen, et al., Immunol. Allerg. Clin. North. Am. 10: 607-637 (1990). It is also known that some epithelial cell type cancers are poorly susceptible to CTLs in vitro, thus precluding routine analysis. These problems have stimulated the art to develop additional methodologies for identifying cancer associated antigens. One key methodology is described by Sahin, et al., Proc. Natl. Acad. Sci. USA 92: 11810-11913 (1995), incorporated by reference. Also, see U.S. Patent Applications Serial No. 08/580,980, now U.S. Patent No. 5,698,396 and Application Serial No. 08/479,328, filed on June 7, 1995 and January 3, 1996, respectively. All three of these references are incorporated by reference. To summarize, the method involves the expression of cDNA libraries in a prokaryotic host. (The libraries are secured from a tumor sample). The expressed libraries are then immunoscreened with absorbed and diluted sera, in order to detect those antigens which elicit high titer humoral responses. This methodology is known as the SEREX method ("Serological identification of antigens by Recombinant Expression Cloning"). The methodology has been employed to confirm expression of previously identified tumor associated antigens, as well as to detect new ones. See the above referenced patent applications and Sahin, et al., supra, as well as Crew, et al, EMBO J 144: 2333-2340 (1995). The SEREX methodology has been applied to esophageal cancer samples, and an esophageal cancer associated antigen has now been identified, and its encoding nucleic acid molecule isolated and cloned, as per U.S. patent application Serial No. 08/725,182, filed October 3, 1996, incorporated by reference herein . The relationship between some of the tumor associated genes and a triad of genes, known as the SSX genes, is under investigation. See Sahin, et al., supra; and Tureci, et al., Cancer Res 56:4766-4772 (1996). One of these SSX genes, referred to as SSX2, was identified, at first, as one of two genes involved in a chromosomal translocation event (t(X; 18)(p 11.2; q 11.2)), which is present in 70% of synovial sarcomas. See Clark, et al., Nature Genetics 7:502-508 (1994); Crew et al., EMBO J 14:2333-2340 (1995). This gene was later found to be expressed in a number of tumor cells, and is now considered to be a tumor associated antigen referred to as HOM-MEL-40 by Tureci, et al, supra. Its expression to date has been observed in cancer cells, and normal testis only. This parallels other members of the "CT" family of tumor antigens, since they are expressed only in cancer and testis cells. Crew et al. also isolated and cloned the SSX1 gene, which has 89% nucleotide sequence homology with SSX2. See Crew et al., supra. Additional work directed to the identification of SSX genes has resulted in the identification of SSX3, as is described by DeLeeuw, et al, Cytogenet. Genet 73:179-183 (1996). The fact that SSX presentation parallels other CT antigens suggested to the inventors that other SSX genes might be isolated. Application of a modification of the SEREX technology described supra has been used, together with other techniques, to clone two, additional SSX genes, referred to as SSX4 and SSX5 as well as an alternate splice variants of the SSX4 gene. This work is described in U.S. Serial No. 08/851,138, filed May 5, 1997, incorporated by reference, as well as by Chen, et al., Proc. Natl. Acad. Sci USA 94: 1914-1918 (1997), also incorporated by reference. The fact that many markers were found in both normal testis and tumor cells, but not other normal cells, suggested that further investigation in this area might uncover additional related molecules. The diversity of those discovered so far, however, did not provide any guidance as to the characteristics of the additional molecules which might be found. Most of the work prior to the invention disclosed herein, used cDNA libraries obtained from cancer cells. As will be developed herein, it has now been shown that such molecules can also be determined using a non-transformed, or normal cell source for the cDNA libraries previously obtained from cancer cells. This is quite surprising, as it might well be assumed that tumor markers are expressed only in tumor cells. This has now been shown to not be the case. Exemplary of a normal cell library which can be used is a testis cell library screened against various serum samples, such as autologous serum. The SEREX methodology, as described supra, has proven to be very useful in identifying molecules of interest. The inventors have found, however, that it is not an ideal method when short cDNA molecules are the ones of interest in a given library. One aspect of the invention described herein is a method for identifying short cDNA molecules which are of interest in connection with pathologies of the type discussed herein. Synaptonemal complex protein 1 ("SCP1" hereafter) is a protein involved in the meiotic prophase of spermatocytes. The gene which encodes murine SCP1 has been mapped to chromosome lp.12-p.13. See Sage, et al, Biochem. Biophys. Acta 1263: 258- 260 (1995) incorporated by reference. The human form of SCP1 has been reported to be expressed only in testis. See Meuwissen, et al, EMBO J 11:5091-5100 (1992), incorporated by reference. Meuwissen et al, supra describe SCP1 protein as a major component of the synaptonemal complex, a tripartite, macromolecular assembly which is formed between homologous chromosomes during meiotic prophase. See Wettstein, et al, Annu. Rev. Genet 3:331-413 (1984); Heyting, et al, Genome 31 :81-89 (1986). More details of the protein may be found e.g., in Meuwissen, et al, Genomics 37:101-106 (1997); Gillies, et al, Curr. Trac. Lab. Carlsberg 40:135-161 (1975); Schmekel, et al, Exp. Cell Res 226:20- 30 (1996); Moses, et al, Symp. Soc. Exp. Biol. 38:245-270 (1984); Carpenter, Bioessays 6:232-236 (1987); Loidl, et al, Genome 33:759-778 (1990); Moens, Bioessays 16:101-106 (1994); Roeder, Trends Genet 6:385-389 (1990). The location of the gene for SCP1 is different than that for all previously identified cancer testis antigens (CTAs), which map to the X chromosome. It has been found, that SCP1 is expressed in tumor cells, especially in renal cell carcinomas, gliomas, and breast carcinomas, but not in normal cells except for testis. Hence, it serves as a CTA but differs in that it possesses strong expression not only in melanoma, but in those tumor types listed supra. This is significant in terms of both diagnostic and therapeutic approaches to transformed cells, as will be seen from the disclosure which follows. The fact that the molecule is also involved in normal meiosis suggests an important correlation between the molecule, chromosomal replication, cell division, and the onset of oncogenesis. Detailed Description of Preferred Embodiments Example 1 Experiments were carried out to identify and to isolate cDNA corresponding to mRNA found exclusively in testis, and hence genes expressed only in testis cells. To do this, the methodology described by Diatchenko et al, Proc. Natl. Acad. Sci USA 93:6025- 6030 (1996), incorporated by reference, was used to generate cDNA fragments specifically expressed in human testis cells, which had been obtained from biopsies of tumor free patients. Specifically, two mg of mRNA was taken from each of two, different testicular tissue specimens, and was used as a tester probe. Driver cDNA was obtained by synthesizing cDNA from mRNA taken from ten healthy tissue specimens (colon, stomach, brain, resting and activated peripheral blood mononuclear cells, skeletal muscle, liver, kidney, lungs and skin). Diatchenko, et al, supra, was followed to carry out suppression subtractive hybridization PCR, after tester and driver cDNA were permitted to hybridize. The resulting, isolated fragments were then used to isolate full length transcript. To do this, a cDNA phagemid library was constructed, using the same cDNA (i.e., the normal testis library), using 5 mg of mRNA. A library of 4 x 10 6 primary clones was produced and, following standard isolation procedures, the phagemid library was hybridized onto nitrocellulose membranes and then blotted with the fragments obtained previously. Following blotting, the membranes were washed, and any phagemids which had bound to immobilized cDNA were eluted. The eluted, full length molecules were used to prepare double stranded cDNA, using known methods, and the cDNA was then re-ligated into precut vectors, and then used for transfections and amplification. An expression library of 400,000 recombinants resulted. Example 2 Following the creation of the expression library described supra, immune screening experiments were carried out to determine if any IgGs against the expression products of the library were present in serum from a tumor patient. To do this, a serum sample of a patient with renal cell cancer was diluted, 1 :100, and then screened against 200,000 of the recombinants, following Tureci, et al, Cancer Res 56:4766-4772 (1996), and U.S. Patent Serial No. 5,698,396, both of which are incorporated by reference. Reactive clones were visualized by incubation with an anti-human, Fc specific, alkaline phosphatase labelled antibody, which was then developed with the dye 5-bromo-4-chloro-3-indolyl phosphate, and nitroblue tetrazolium, following known methods. Of the 200,000 clones screened, five were positive. Three of these were found to be identical to part of a previously identified protein, i.e., SCPl, a protein whose expression has been linked, specifically to the meiotic prophase of spermatocytes, and which has been linked to the pairing of homologous chromosomes, which is essential to the generation of haploid cells in meioses I. The three positive clones were sequenced and found to correspond to nucleotides 726- 2401, 147-2728, and 634-2462 of SCPl, but for changes at amino acid positions 225 where CAT was replaced by TTT leading to F instead of H, and at position 226, glycine was replaced by glutamine (GGG was replaced by GAG). This represents changes at nucleotides 716, 767, 768 and 771. There is a change at position 208, but it is a silent mutation. The sequence of SCPl is set forth as SEQ ID NO 1 and is found in Meuwissen et al., Genomics 37: 101-106 (1997) incorporated by reference. Example 3 Experiments were then carried out to determine whether or not the SCPl molecule was being expressed by normal tissues. This was determined via Northern blotting, and via RT-PCR. Northern blotting followed Chomczynsky, et al. Anal. Biochem 72:248-254 (1976), incorporated by reference. To elaborate, mRNA was removed from various tissue samples, checked for integrity via electrophoresis in formalin/MOPS gels, and then 10 mg from each sample were blotted onto nylon membranes, prehybridized, and then incubated with a 32 P labelled cDNA probe which consisted of nucleotides 2715-3264 of SCPl (SEQ ID No: 1). Specifically the probes were hybridized overnight at 42°C in a solution of 50% formamide 6 x SSC, 5 x Denhardt's, and 0.2% SDS. Membranes were then washed at progressively higher stringencies, with the final wash at 1 x SSC, 0.2% SDS at 65°C. Autoradiography was conducted at -70°C, for up to 7 days. To carry out RT-PCR, total RNA was extracted, primed with an oligo-dT (18) nucleotide, and then reverse transcribed. Primers used were: 5' - GTACAGCAGA AAGCAAGCAA CTGAATG (SEQ ID NO: 2) and 5 r - GAAGGAACTG CTTTAGAATC CAATTTCC-3' (SEQ ID NO: 3). The expected primer product size was 564 base pairs. The only normal tissue sample to test positive was testis. The RT-PCR protocol set forth supra was also used on tumor tissue samples. These results are set forth in the Table which follows. Northern blotting confirmed the work for renal, breast, and glioma tumor samples. Example 4 The analysis discussed, supra, was carried forward with Southern blotting, in accordance with Maniatis, et al, Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, 1982). In brief, the endonuclease Hae III was used on DNA extracted from testis and peripheral blood lymphocytes. Equal amounts of sample were checked by staining, visualized under UV light, and then were hybridized with full length cDNA for SCPl at 6xSSC, 4x Denhardt's and 0.5% SDS, followed by washing and auto-radiography as described above. The banding patterns which resulted suggested a gene family, rather than a single gene. Example 5 A final set of experiments was then carried out to test for presence of the SCPl protein. This was done by Western blotting. SCPl specific rabbit antiserum, described by Schmekel et al, Chromosoma 102: 682-692 (1993), incorporated by reference, was used. Cell lysates (10 ug, per lane), were mixed with 2 x SDS sample buffer (0.1 M Tris- HC1, pH 6.8, 0.2M dithiothreitol, 4% SDS, 0.2% bromophenol blue, 20% glycerol), electrophoresed on 12% SDS gels, via PAGE, and were then blotted to nylon membranes. The membranes were blocked with 5% non-fat milk in TBS for 1 hour, to address nonspecific binding, and the membranes were then incubated with 1:100 diluted rabbit -anti SCPl antiserum. The blots were then incubated for 1 hour with alkaline phosphatase conjugated anti-IgG. Membranes were washed extensively with TBS and 0.01%) Tween, following each incubation. Positive reactions were monitored in the same fashion as is described, supra. A 125 kDa protein was detected in lysates of normal testis cells and tumor cells, but in no other samples, indicating that SCPl functions as a marker for tumor cells. Example 6 The amino acid sequence of the protein encoded by the SCP-1 gene was analyzed for peptide sequences which correspondence to HLA binding motifs. This was done using the algorithm taught by Parker et al., J. Immunol. 142: 163 (1994), incorporated by reference. In the Table which follows , the amino acid sequence, the HLA molecule to which it presumably binds, and the positions in SCP-1 are given. The resulting complexes should provoke a cytolytic T cell response. This could be determined by one skilled in the art following methods taught by, e.g., van der Bruggen, et al., J. Eur. J. Immunol. 24: 3038-3043 (1994), incorporated by reference. MHC MOLECULE PEPTIDE POSITION Al NSEGLSRVY 98-106 Al SSELEEMTK 416-424 Al EVELEELKK 430-438 MHC MOLECULE PEPTIDE POSITION Al CTEDDFEFPF 41-50 Al NIDSDPALQK 61-70 Al RTEQQRLENY 392-401 Al IADEAVKLQK 685-694 Al lAEMVALMEK 704-713 A2 KLYKEAEKI 108-116 A2 KLQENRKII 133-141 A2 KMITAFEEL 220-228 A2 VVTEFETTV 376-384 A2 VELEELKKV 431-439 A2 VLGEKETLL 439-447 A2 LLQAREKEV 470-478 A2 RMLTQIENL 554-562 A2 NLQETETQL 561-569 A2 QLNVYEIKV 632-640 A2 NLLEEVEKA 674-682 A2 KMREDRWAV 947-955 A2 ALQKVNFLPV 67-76 A2 FLLEESRDKV 287-296 A2 KLTHJKEVEL 424-433 A2 KQFEKIAEEL 451-460 A2 GLLQAREKEV 469-478 A2 TQLRNELEYV 567-576 A2 KQVENKNKYI 603-612 A2 KQLNVYEIKV 631-640 A2 NVYEIKVNKL 634-643 A2 YLWTSAKNTL 835-844 A2 KLKEAEKLFV 964-973 MHC MOLECULE PEPTIDE POSITION A3 KLSSKRELK 502-510 A3 NLRKQVENK 600-608 A3 TLGGDSTFFK 27-36 A3 KLYKEAEKIK 108-117 A3 KMITAFEELR 220-229 A3 LLYDNKQFEK 446-455 A3 KLELELESAK 642-651 A3 LLETPDIYWK 797-806 A24 VYMDLNSNI 210-218 A24 NYEDQLIIL 400-408 A24 VYEIKVNKL 635-643 A24 LYDNKQFEKI 447-456 B7 AQRKAIQEL 143-151 B7 ATRHLCNLL 178-186 B7 TPKKAPSSL 925-933 B7 DPALQKVNFL 65-74 B7 QAREKEVHDL 472-481 B7 LPKRGQRPKL 494-503 B7 RPKLSSKREL 500-509 B7 KPKLQQRENL 859-868 B8 ELRQKESKL 126-143 B8 ESRDKVNQL 291-299 B8 SAKQKFGEI 649-657 B8 ISKDKRDYL 828-836 MHC MOLECULE PEPTIDE POSITION B8 IAKMDRKKKL 956-965 B35 ISKDKRDY 828-835 (S B35 TPKKAPSSL 925-933 B35 LPKRGQRPKL 494-503 B35 RPKLSSKREL 500-509 B35 KSKEQEQSSL 733-742 B35 KPKLQQRENL 859-868 B44 TEDDFEFPF 42-50 B44 KEAEKIKKW 111-119 B44 AEKTKKYEY 194-202 B44 TEQQRLENY 393-401 B44 RELKNTEYF 507-515 B44 AESKQLNVY 628-636 B44 EEETLKTLY 903-911 B44 YEREETRQVY 202-211 B44 AENSRLEMHF 232-241 B44 KENKMKDLTF 278-287 B44 REKEVHDLEY 474-483 B44 KEVHDLEYSY 476-485 B44 DEVKCKLDKS 585-594 B44 LELESAKQKF 645-654 B44 EERKSELGLY 723-732 B44 SEEETLKTLY 902-911 MHC MOLECULE PEPTIDE POSITION B52 KQKPFALFV 3-11 B52 LQIATNTIC 345-353 B52 ENYEDQLII 399-407 B52 CQHKIAEMV 700-708 B52 LQKVNFLPVL 68-77 The foregoing examples demonstrate several features of the invention. These include diagnostic methods for determining presence of transformed cells, such as cancer cells, in a sample. The examples show that there is a family of SCP genes, such as SCP- 1. Hence, the invention involves, inter alia, detecting an SCP protein or mRNA for an SCP gene in a sample taken from a source other than testis, wherein presence of either or both of these is indicative of a pathology, such as cancer or some other type of transformed cells. Exemplary of the type of diagnostic assays which can be carried out are amplification assays such as polymerase chain reaction, or immunoassays. It is especially preferred to assay for SCP-1, as a determination of breast cancer, ovarian cancer, renal cell carcinoma, or glioma. The SCP proteins, as indicated, have been associated, exclusively, with meiosis. As a rule, cells other than germ cells do not undergo meiosis. Hence, the expression of SCP proteins such as SCP-1 in a context other than germ cells undergoing meiosis is clearly an indication of an abnormality. It is believed that expression of SCP proteins may contribute to the genetic instability of cancer cells, leading to abnormalities such as aneuploidy, manifesting the phenomenon in early neoplastic change. One aspect of the invention, then, is a method for determining presence of an abnormal condition by assaying for an SCP protein, or a peptide derived from the protein, wherein the presence of the protein at all, or an abnormal level of the protein (which may include its presence), is indicative of an abnormality, such as cancer. There are many ways to carry out this type of assay. For example, as indicated herein, antibodies to the protein were found in patient samples. One can assay for these antibodies using, e.g., the methodology described herein, or by using a purified SCP protein or antigenic fragment thereof, and so forth. One can also assay for the protein itself, using antibodies, which may be isolated from samples, or generated using an SCP protein and standard techniques. This antibodies can then be labelled, if desired, and used in standard immunoassays. Similarly, any and all nucleic acid hybridization systems can be used, including amplification assays, such as PCR, basic probe hybridization assays, and so forth. The antibodies, such as polyclonal antibodies, monoclonal antibodies, the hybridomas which produce them, recombinantly produced antibodies, binding fragments of these, hybridization kits, DNA probes, and so forth, are all additional features of the invention. Any one of these can also be used in progression/regression studies. Since it is clear that a low or non-existent level of expression of SCP protein is found in normal cells, one can monitor the course of abnormality involving expression of SCP, simply by monitoring levels of the protein, its expression, and so forth using any or all of the methods set forth supra. It should be clear that these methodologies may also be used to track the efficacy of a therapeutic regime. Essentially, one can take a baseline value for the SCP protein or proteins being tested, using any of the assays discussed supra, administer a given therapeutic agent, and then monitor levels of the protein thereafter, observing changes in SCP levels as indicia of the efficacy of the regime. Regarding the progression/regression studies. One can monitor the course of an abnormality involving expression of SCP- 1 simply by monitoring levels of protein, its expression, antibodies against it and so forth using any or all of the methods set forth supra. It should be clear that these methodologies may also be used to track the efficacy of a therapeutic regime. Essentially, one can take a baseline value for the SCP-1 protein, using any of the assays discussed supra, administer a given therapeutic agent, and then monitor levels of the protein, using any of the assays discussed supra, administer a given therapeutic agent, and then monitor levels of the protein thereafter, observing changes in SCP-1 levels as indicia of the efficacy of the regime. One can monitor these levels using, e.g., tetrameric peptide structures, such as structures based on the disclosures of Braud, et al., Nature 391 795-799 (1998); Altaian, et al., Science 274: 94-96 (1996), and U.S. Patent application Serial No. 09/049,850, filed March 27, 1998, all of which are incorporated by reference. The identification of SCP proteins as being implicated in pathological conditions such as cancer also suggests a number of therapeutic approaches to such conditions. The experiments set forth supra establish that antibodies are produced in response to expression of the protein, suggesting its use as a vaccine. Hence, a further embodiment of the invention is the treatment of conditions which are characterized by aberrant or abnormal levels of one or more SCP proteins, via immunotherapeutic approaches. One of these approaches is the administration of an amount of an SCP protein, or an immunogenic peptide derived from the protein in an amount sufficient to provoke or augment an immune response. The protein or peptide may be combined with one or more of the known immune adjuvants, costimulatory molecules, or MHC helper binding peptides, such as saponins, GM-CSF, interleukins, LIF-3, emulsifying oils such as vitamin E, heat shock proteins and so forth. If the peptides are too small to generate a sufficient antibody response, they can be coupled to the well known conjugates used to stimulate responses. Similarly, the immunotherapeutic approaches include administering an amount of inhibiting antibodies sufficient to inhibit the SCP protein. These antibodies may be, e.g., antibodies produced via any of the standard approaches elaborated upon supra. T cell responses may also be elicited by using peptides derived from the SCP proteins which then complex, non-covalently, with MHC molecules, thereby stimulating proliferation of cytolytic T cells against any such complexes in the subject. It is to be noted that the T cells may also be elicited in vitro using immune responsive cells such as dendritic cells, lymphocytes, or any other immune responsive cells, and then reperfused into the subject being treated. Note that the generation of T cells and/or antibodies can also be accomplished by administering cells, preferably treated to be rendered non-proliferative, which present relevant T cell or B cell epitopes for response. The therapeutic approaches may also include gene therapies, wherein an antisense molecule, preferably from 10 to 100 nucleotides in length, is administered to the subject either "neat" or in a carrier, such as a liposome, to facilitate incorporation into a cell, followed by inhibition of expression of the protein. Such antisense sequences may also be incorporated into appropriate vaccines, such as in viral vectors (e.g., Vaccinia), bacterial constructs, such as variants of the well known BCG vaccine, and so forth. An additional DNA based therapeutic approach is the use of a vector which comprises one or more nucleotide sequences, preferably a plurality of these, each of which encodes an immunoreactive peptide derived from the expressed proteins. One can combine these peptide expressing sequences in all possible variations, such as one from each protein, several from one or more protein and one from each of the additional proteins, a plurality from some and none from others, and so forth. Other therapeutic approaches include the administration of SCP- 1 proteins per se, one or more antigenic peptides derived therefrom, such as those presented in Example 6, as well as so-called polytopic vaccines. These include a plurality of antigenic peptides, such as those in Example 6, united together, preferably by linker sequences. The resulting peptides may bind to either MHC-Class I or Class II molecules. These proteins, peptides, or polytopic vaccines may be administered in combination with an appropriate adjuvant, costimulatory molecule, or binding helper peptide. They may also be administered in the form of genetic constructs which are designed to permit expression of the protein, the peptide, the polytopic structures, etc. Peptides and polytopic structures can be expressed by so-called "minigenes" i.e., DNA molecules designed to express portions of the entire SCP-1 molecule, or the various portions of the molecules, linked together as described supra. The amount of agent administered and the manner in which it is administered will, vary, based on the condition being treated and the individual. Standard forms of administration, such as intravenous, intradermal, subcutaneous, oral, rectal and transdermal administration can be used. With respect to formulations, the proteins and or peptides may be combined with adjuvant and/or carriers such as a saponin, GM-CSF, one or more interleukin, vitamin E, FLT-3, one or more heat shock protein, etc. When the nucleic acid approach is utilized, various vectors, such as Vaccinia or adenovirus based vectors can be used. Any vector useful in eukaryotic transfection, such as in transfection of human cells, can be used. These vectors can be used to produce, e.g., cells such as dendritic cells which present relevant peptide/MH complexes on their surface. The cells can then be rendered non-proliferative prior to their administration, using standard methodologies. Polytopes, as used herein, are groups of two or more potentially immunogenic or immune stimulating peptides, which can be joined together in various ways, to determine if this type of molecule will stimulate and/or provoke an immune response. These peptides can be joined together directly, or via the use of flanking sequences. See Thompson et al. Proc. Natl. Acad. Sci USA 92(13): 5845-5849 (1995), teaching the direct linkage of relevant epitopic sequences. The use of polytopes as vaccines is well known. See, e.g., Gilbert et al.., Nat Biotechnol. 15(12): 1280-1284 (1997); Thomson et al, supra; Thomson et al, J. Immunol. 157(2): 822-826 (1996); Tam et al., J. Exp. Med. 171(1): 299-306 (1990), all of which are incorporated by reference. The Tam reference in particular shows that polytopes, when used in a mouse model, are useful in generating both antibody and protective immunity. Further, the reference shows that the polytopes, when digested, yield peptides which can be and are presented by MHCs. Tam shows this by showing recognition of individual epitopes processed from polytope 'strings' via CTLs. This approach can be used, e.g., in determining how many epitopes can be joined in a polytope and still provoke recognition and also to determine the efficacy of different combinations of epitopes. Different combinations may be 'tailor- made' for the patients expressing particular subsets of tumor rejection antigens. These polytopes can be introduced as polypeptide structures, or via the use of nucleic acid delivery systems. To elaborate, the art has many different ways available to introduce DNA encoding an individual epitope, or a polytope such as is discussed supra. See, e.g., Allsopp et al., Eur J. Immunol. 26(8); 1951-1959(1996), incorporated by reference. Adenovirus, pox-virus, Ty-virus like particulars, plasmids, bacteria, etc., can be used. One can test these systems in mouse models to determine which system seems most appropriate for a given, parallel situation in humans. They can also be tested in human clinical trials. Also a feature of the invention are the mutein forms of SCP-1 and the nucleic acid molecule encoding it, as described supra. These muteins can be used in the same way SCP molecules can be used. The invention also involves a method for determining substances produced by a subject capable of eliciting an immune response, wherein one produces a cDNA library of a normal cell taken from a subject, such as a testis cell, inserting the cDNA molecules of the library into an expression vector, transfecting the vector into host cells to produce transfected host cells and then culturing the transfected host cell to express the substance of interest. Following this, the cells are lysed to form a lysate, which is then contacted with a sample of a body fluid taken from a subject, which contains an immuno logic binding partner for the immunoreactive substance. This step removes any immunologic binding partner from said sample which is specific for non-transfected host cells. The resulting sample is then contacted to a sample of lysed host cells transfected with the same vector which does not contain any library cDNA which removes any immunologic binding partners specific for vector produced antigens. Then, the sample is contacted to the lysate so that any binding partners specific substance bind thereto, after which one determines whether or not any binding partners have, in fact, bound to such substances, so as to determine said immunoreactive substance. This method is similar to that described in U.S. Patent No. 5,698,396, except that the source of the library is a normal cell, such as a testis cell. As the examples, supra, indicate, this type of library was used to identify the tumor antigen. The body fluid sample may be taken from the same subject from whom the testis cells are taken (autologous serum), or it may be from a different individual. As in the 08/580,980 application, the cDNA so identified may be isolated, as can the binding partner. Relevant host cells for transformation may be eukaryotic, or prokaryotic, such as E. coli, and the expression vectors may be any of the standard expression vectors, such as a viral vector, a phage vector, and so forth. The sample used may be any of the sample types used in biological analysis, such as serum, blood cerebrospinal fluid, urine, stool samples, tissue samples such as skin, and so forth. Various types of antigens can be identified in this way, such as cancer associated antigens, autoimmune antigens, antigen associates with pathogens, such as viruses, and so forth. The methodology is conveniently carried out by, inter alia, immobilizing the lysate described supra to, e.g., a membrane, such as a nylon or a cellulose membrane. Other features of the invention will be clear to the skilled artisan, and need not be repeated here. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, it being recognized that various modifications are possible within the scope of the invention. (1) GENERAL INFORMATION: (i) APPLICANTS: Tureci, Ozlem; Sahin, Ugur; Pfreundschuh, Michael (ii) TITLE OF INVENTION: Methods For Diagnosis And Treating Cancers, And Methods For Identifying Pathogenic Markers In A Sample Of Normal Cells (iii) NUMBER OF SEQUENCES: 3 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Felfe & Lynch (B) STREET: 805 Third Avenue (C) CITY: New York City (D) STATE: New York (F) ZIP: 10022 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Diskette, 3.5 inch, 144 kb storage (B) COMPUTER: IBM (C) OPERATING SYSTEM: PC-DOS (D) SOFTWARE: Wordperfect (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: 08/892,702 (B) FILING DATE: 15-July-1997 (C) CLASSIFICATION: 435 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Hanson, Norman D. (B) REGISTRATION NUMBER: 30,946 (C) REFERENCE/DOCKET NUMBER: LUD 5491 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (212) 688-9200 (B) TELEFAX: (212) 838-3884 (2) INFORMATION FOR SEQUENCE ID NO: 1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3393 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS : dobule (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1: GCCCTCATAG ACCGTTTGTT GTAGTTCGCG TGGGAACAGC AACCCACGGT TTCCCGATAG 60 TTCTTCAAAG ATATTTACAA CCGTAACAGA GAAAATGGAA AAGCAAAAGC CCTTTGCATT 120 GTTCGTACCA CCGAGATCAA GCAGCAGTCA GGTGTCTGCG GTGAAACCTC AGACCCTGGG 180 AGGCGATTCC ACTTTCTTCA AGAGTTTCAA CAAATGTACT GAAGATGATT TGGAGTTTCC 240 ATTTGCAAAG ACTAATCTCT CCAAAAATGG GGAAAACATT GATTCAGATC CTGCTTTACA 300 AAAAGTTAAT TTCTTGCCCG TGCTTGAGCA GGTTGGTAAT TCTGACTGTC ACTATCAGGA 360 AGGACTAAAA GACTCTGATT TGGAGAATTC AGAGGGATTG AGCAGAGTGT TTTCAAAACT 420 GTATAAGGAG GCTGAAAAGA TAAAAAAATG GAAAGTAAGT ACAGAAGCTG AACTGAGACA 480 GAAAGAAAGT AAGTTGCAAG AAAACAGAAA GATAATTGAA GCACAGCGAA AAGCCATTCA 540 GGAACTGCAA TTTGGAAATG AAAAAGTAAG TTTGAAATTA GAAGAAGGAA TACAAGAAAA 600 TAAAGATTTA ATAAAAGAGA ATAATGCCAC AAGGCATTTA TGTAATCTAC TCAAAGAAAC 660 CTGTGCTAGA TCTGCAGAAA AGACAAAGAA ATATGAATAT GAACGGGAAG AAACCAGGCA 720 AGTTTATATG GATCTAAATA ATAACATTGA GAAAATGATA ACAGCTCATG GGGAACTTCG 780 TGTGCAAGCT GAGAATTCCA GACTGGAAAT GCATTTTAAG TTAAAGGAAG ATTATGAAAA 840 AATCCAACAC CTTGAACAAG AATACAAGAA GGAAATAAAT GACAAGGAAA AGCAGGTATC 900 ACTACTATTG ATCCAAATCA CTGAGAAAGA AAATAAAATG AAAGATTTAA CATTTCTGCT 960 AGAGGAATCC AGAGATAAAG TTAATCAATT AGAGGAAAAG ACAAAATTAC AGAGTGAAAA 1020 CTTAAAACAA TCAATTGAGA AACAGCATCA TTTGACTAAA GAACTAGAAG ATATTAAAGT 1080 GTCATTACAA AGAAGTGTGA GTACTCAAAA GGCTTTAGAG GAAGATTTAC AGATAGCAAC 1140 AAAAACAATT TGTCAGCTAA CTGAAGAAAA AGAAACTCAA ATGGAAGAAT CTAATAAAGC 1200 TAGAGCTGCT CATTCGTTTG TGGTTACTGA ATTTGAAACT ACTGTCTGCA GCTTGGAAGA 1260 ATTATTGAGA ACAGAACAGC AAAGATTGGA AAAAAATGAA GATCAATTGA AAATACTTAC 1320 CATGGAGCTT CAAAAGAAAT CAAGTGAGCT GGAAGAGATG ACTAAGCTTA CAAATAACAA 1380 AGAAGTAGAA CTTGAAGAAT TGAAAAAAGT CTTGGGAGAA AAGGAAACAC TTTTATATGA 1440 AAATAAACAA TTTGAGAAGA TTGCTGAAGA ATTAAAAGGA ACAGAACAAG AACTAATTGG 1500 TCTTCTCCAA GCCAGAGAGA AAGAAGTACA TGATTTGGAA ATACAGTTAA CTGCCATTAC 1560 CACAAGTGAA CAGTATTATT CAAAAGAGGT TAAAGATCTA AAAACTGAGC TTGAAAACGA 1620 GAAGCTTAAG AATACTGAAT TAACTTCACA CTGCAACAAG CTTTCACTAG AAAACAAAGA 1680 GCTCACACAG GAAACAAGTG ATATGACCCT AGAACTCAAG AATCAGCAAG AAGATATTAA 1740 TAATAACAAA AAGCAAGAAG AAAGGATGTT GAAACAAATA GAAAATCTTC AAGAAACAGA 1800 AACCCAATTA AGAAATGAAC TAGAATATGT GAGAGAAGAG CTAAAACAGA AAAGAGATGA 1860 AGTTAAATGT AAATTGGACA AGAGTGAAGA AAATTGTAAC AATTTAAGGA AACAAGTTGA 1920 AAATAAAAAC AAGTATATTG AAGAACTTCA GCAGGAGAAT AAGGCCTTGA AAAAAAAAGG 1980 TACAGCAGAA AGCAAGCAAC TGAATGTTTA TGAGATAAAG GTCAATAAAT TAGAGTTAGA 2040 ACTAGAAAGT GCCAAACAGA AATTTGGAGA AATCACAGAC ACCTATCAGA AAGAAATTGA 2100 GGACAAAAAG ATATCAGAAG AAAATCTTTT GGAAGAGGTT GAGAAAGCAA AAGTAATAGC 2160 TGATGAAGCA GTAAAATTAC AGAAAGAAAT TGATAAGCGA TGTCAACATA AAATAGCTGA 2220 AATGGTAGCA CTTATGGAAA AACATAAGCA CCAATATGAT AAGATCATTG AAGAAAGAGA 2280 CTCAGAATTA GGACTTTATA AGAGCAAAGA ACAAGAACAG TCATCACTGA GAGCATCTTT 2340 GGAGATTGAA CTATCCAATC TCAAAGCTGA ACTTTTGTCT GTTAAGAAGC AACTTGAAAT 2400 AGAAAGAGAA GAGAAGGAAA AACTCAAAAG AGAGGCAAAA GAAAACACAG CTACTCTTAA 2460 AGAAAAAAAA GACAAGAAAA CACAAACATT TTTATTGGAA ACACCTGAAA TTTATTGGAA 2520 ATTGGATTCT AAAGCAGTTC CTTCACAAAC TGTATCTCGA AATTTCACAT CAGTTGATCA 2580 TGGCATATCC AAAGATAAAA GAGACTATCT GTGGACATCT GCCAAAAATA CTTTATCTAC 2640 ACCATTGCCA AAGGCATATA CAGTGAAGAC ACCAACAAAA CCAAAACTAC AGCAAAGAGA 2700 AAACTTGAAT ATACCCATTG AAGAAAGTAA AAAAAAGAGA AAAATGGCCT TTGAATTTGA 2760 TATTAATTCA GATAGTTCAG AAACTACTGA TCTTTTGAGC ATGGTTTCAG AAGAAGAGAC 2820 ATTGAAAACA CTGTATAGGA ACAATAATCC ACCAGCTTCT CATCTTTGTG TCAAAACACC 2880 AAAAAAGGCC CCTTCATCTC TAACAACCCC TGGACCTACA CTGAAGTTTG GAGCTATAAG 2940 AAAAATGCGG GAGGACCGTT GGGCTGTAAT TGCTAAAATG GATAGAAAAA AAAAACTAAA 3000 AGAAGCTGAA AAGTTATTTG TTTAATTTCA GAGAATCAGT GTAGTTAAGG AGCCTAATAA 3060 CGTGAAACTT ATAGTTAATA TTTTGTTCTT ATTTGCCAGA GCCACATTTT ATCTGGAAGT 3120 TGAGACTTAA AAAATACTTG CATGAATGAT TTGTGTTTCT TTATATTTTT AGCCTAAATG 3180 TTAACTACAT ATTGTCTGGA AACCTGTCAT TGTATTCAGA TAATTAGATG ATTATATATT 3240 GTTGTTACTT TTTCTTGTAT TCATGAAAAC TGTTTTTACT AAGTTTTCAA ATTTGTAAAG 3300 TTAGCCTTTG AATGCTAGGA ATGCATTATT GAGGGTCATT CTTTATTCTT TACTATTAAA 3360 ATATTTTGGA TGCAAAAAAA AAAAAAAAAA AAA 3393 (2) INFORMATION FOR SEQUENCE ID NO: 2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: GTACAGCAGA AAGCAAGCAA CTGAATG 27 (2) INFORMATION FOR SEQUENCE ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: GAAGGAACTG CTTTAGAATC CAATTTCC 28

Claims: Claims 1. A method for determining presence of a transformed cell, comprising assaying a sample of cells taken from tissue other than testis for expression of a member of the SCP gene family, wherein expression thereof is indicative of transformed cells in said sample. 2. The method of claim 1, wherein said member of the SCP gene family is SCP-1. 3. The method of claim 1, comprising determining an antibody specific for said member of the SCP gene family in said sample. 4. The method of claim 1, further comprising determining presence of mRNA for said member of the SCP gene family in said sample. 5. The method of claim 3, comprising determining presence of mRNA via polymerase chain reaction. 6. The method of claim 1, comprising assaying said sample for an SCP protein. 7. The method of claim 1, wherein said SCP protein is SCP-1. 8. The method of claim 5, comprising assaying said sample via an immunoassay. 9. The method of claim 1, wherein said transformed cell is a cancer cell. 10. The method of claim 8, wherein said cancer cell is a renal cancer cell, a glioma, ovarian, or a breast cancer cell. 11. A method for treating a subject afflicted with a disorder characterized by inappropriate amounts of at least one SCP protein, comprising: (i) removing an immune responsive cell containing sample from said subject, (ii) contacting the immune responsive cell containing sample to a cell line transfected with a nucleic acid molecule coding for an SCP protein expressed by abnormal cells associated with said conditions, under conditions favoring production of cytolytic T cells against a peptide derived from said SCP protein, and (iii) introducing said cytolytic T cells to said subject in an amount sufficient to lyse said cells. 12. The method of claim 10 wherein said SCP protein is SCP-1 . 13. A method for treating a subject afflicted with a condition characterized by presentation of a peptide derived from an SCP protein in a complex with an MHC molecule on cell surfaces, comprising: (i) identifying an SCP gene expressed by cells associated with said condition; (ii) identifying an MHC molecule which presents a portion of an expression product of said SCP gene; (iii) transfecting a host cell presenting said MHC molecule said SCP gene; (iv) culturing said transfected cells to express said SCP gene and present said peptide in complexes with said MHC molecule, and; (v) introducing an amount of said cells to said subject sufficient to provoke an immune response against said abnormal cells. 14. The method of claim 12, wherein said immune response comprises a B-cell response. 15. The method of claim 12, wherein said immune response is a T-cell response. 16. The method of claim 13, wherein said B cell response comprises production of antibodies specific to said SCP protein or peptide derived therefrom. 17. The method of claim 14, wherein said T-cell response comprises generation of cytolytic T-cell specific for cells presenting said SCP derived peptide. 18. The method of claim 14, further comprising treating said cells to render them non-proliferative. 19. A method for treating a subject with a condition characterized by abnormal amounts of an SCP protein, comprising: (i) identifying an SCP gene expressed by abnormal cells associated with said condition; (ii) transfecting a host cell having the same MHC type as said patient with said SCP gene; (iii) culturing said transfected cells to express said SCP gene, and; (iv) introducing an amount of said cells to said subject sufficient to provoke an immune response against said abnormal cells. 20. The method of claim 18, further comprising treating said cells to render them non proliferative. 21. A method for treating a subject with a condition characterized by abnormal amounts of an SCP protein, comprising administering to said subject an amount of a cell transfected with (i) a nucleic acid sequence which codes for said SCP protein and (ii) a nucleic acid sequence which codes for an MHC molecule which presents a peptide derived from said SCP protein wherein said peptide is presented by cells associated with said condition, sufficient to alleviate said condition. 22. Method of claim 20, further comprising treating said cell to render it non- proliferative. 23. A method for treating a subject afflicted with a condition characterized by an abnormal amount of an SCP protein, comprising administering to said subject an amount of a reagent consisting essentially of non-proliferative cells having expressed on their surfaces a peptide characteristic of said abnormal cells in an amount sufficient to elicit an immune response thereto. 24. A method for treating a subject afflicted with a condition characterized by an abnormal amount of SCP protein, comprising administering to said subject an antibody which specifically binds to said SCP protein or a peptide derived therefrom, said antibody being coupled to a therapeutically useful agent, in an amount sufficient to treat said condition. 25. A method for treating a subject afflicted with a condition characterized by abnormal amounts of an SCP protein comprising administering to said subject a sample of non-proliferative cells which express an SCP protein in an amount sufficient to alleviate said condition. 26. A method for preventing onset of a condition characterized by abnormal amounts of an SCP protein in a subject comprising administering an amount of a vaccine comprising an SCP protein and an adjuvant in an amount sufficient to prevent onset of said cancerous condition in said subject. 27. A method for preventing onset of a condition characterized by abnormal amounts of an SCP protein in a subject comprising administering an amount of a vaccine comprising a peptide derived from said SCP protein in an amount sufficient to prevent onset of said condition in said subject. 28. A method for preventing onset of a condition characterized by abnormals of an SCP protein in a subject comprising administering an amount of a vector which comprises a gene encoding said SCP protein to a cell which is capable of expressing said protein or presenting a peptide derived therefrom, in an amount sufficient to prevent onset of said cancerous condition in said subject. 29. A method for treating a subject afflicted with a condition characterized by abnormal amounts of an SCP protein, comprising: (i) identifying cells from said subject which express abnormal amounts of said SCP protein; (ii) isolating a sample of said cells; (iii) cultivating said cell, and (iv) introducing said cells to said subject in an amount sufficient to provoke an immune response against said cells. 30. The method of claim 28, further comprising rendering said cells non proliferative, prior to introducing them to said subject. 31. A method for following progress of a therapeutic regime designed to alleviate a condition characterized by abnormal expression of an SCP protein, comprising: (a) assaying a sample from a subject to determine level of a parameter selected from the group consisting of (i) a peptide derived from said SCP protein, (ii) a cytolytic T cell specific for cells presenting said peptide, and (iii) an antibody which specifically binds to said peptide of said SCP protein, at a first time point; (b) assaying level of the parameter selected in (a) at a second point in time and comparing it to the level determined in (a) as a determination of effect of said therapeutic regime. 32. A method for treating a pathological cell condition characterized by aberran expression of an SCP protein associated with said condition, comprising administering to a subject in need thereof an effective amount of either: (a) an SCP protein inhibitor, or (b) an inhibitor of SCP gene expression. 33. The method of claim 31, wherein said SCP protein inhibitor is an inhibiting antibody. 34. The method of claim 31, wherein said inhibitor of SCP gene expression is an antisense molecule. 35. An isolated mutein of SCP-1 protein, said mutein having the amino acid sequence set forth in SEQ ID NO: 1, but has phenylalanine instead of histidine at position 225, and glutamine instead of glycine at position 226. 36. An isolated nucleic acid molecule which encodes for the isolated mutein of claim 33. 37. A method for determining a substance capable of eliciting an immune response, comprising (a) producing a cDNA library from a normal cell taken from a subject, (b) inserting cDNA molecules of said cDNA library into an expression vector, (c) transfecting said expression vector into a host cell to produce a transfected host cell, (d) culturing said transfected host cell to produce said substance, (e) lysing said transformed host cell to form a lysate, (f) contacting said lysate with a sample taken from a subject suspected of having mounted an immune response to said substance to lysed, non-transfected host cells, (g) contacting said sample following (f) to sample of host cells transfected with said vector but no cDNA, (h) contacting said sample following (g) to said lysate, to bind any binding partners for said substance to any of said substances in said lysate, and (i) determining any of said binding to determine said immunoreactive substance. 38. The method of claim 36, wherein said normal cell is a testis cell. 39. The method of claim 36, wherein said sample is serum. 40. The method of claim 36, wherein said sample is taken from the same subject from whom said normal cell is taken. 41. The method of claim 36, wherein said sample is taken from a different subject from whom said normal cell is taken. 42. A composition of matter useful in stimulating an immune response to an SCP protein comprising a plurality of peptides derived from the amino acid sequence of said SCP protein, wherein said peptides bind to one or more MHC molecules presented on the surface of cells which express an abnormal amount of SCP protein. 43. The composition of matter of claim 41, wherein at least a portion of said plurality of peptides bind to MHC molecules and elicit a cytolytic response thereto. 44. The composition of matter of claim 42, further comprising an adjuvant. 45. The composition of matter of claim 43, wherein said adjuvant is a saponin, GM-CSF or interleukin. 46. An isolated antibody which specifically binds to an SCP protein. 47. The antibody of claim 45, wherein said antibody is a monoclonal antibody. 48. The antibody of claim 46, wherein said monoclonal antibody is a humanized monoclonal antibody. 49. The antibody of claim 45, wherein said SCP protein is SCP-1. 50. The antibody of claim 48, wherein said antibody is a monoclonal antibody. 51. An isolated antibody which specifically binds to a peptide derived from an SCP protein. 52. The antibody of claim 50, wherein said antibody is a monoclonal antibody. 53. An isolated antibody which specifically binds to a complex of (i) a peptide derived from an SCP protein and (ii) an MHC molecule to which said peptide comprises, but does not bind to (i) or (ii) alone. 54. The antibody of claim 52, wherein said antibody is a monoclonal antibody. 55. Method for determining regression, progression or onset of a condition characterized by abnormal levels of an SCP protein comprising monitoring a sample from a patient with said condition for a parameter selected from the group consisting of (i) SCP protein, (ii) a peptide derived from said SCP protein and (iii) cytolytic T cells specific for a peptide derived from said protein and an MHC molecule to which it is bound and is indicative of progression or regression or onset of said condition. 56. The method of claim 54, wherein said sample is a body fluid. 57. The method of claim 54, wherein said sample is a tissue. 58. The method of claim 54, wherein contacting said sample with an antibody which specifically binds with said SCP protein or peptide. 59. The method of claim 57, wherein said antibody is labelled with a radioactive label or an enzyme. 60. The method of claim 57, wherein said antibody is a monoclonal antibody. 61. The method of claim 54, comprising amplifying RNA which codes for said SCP protein. 62. The method of claim 60, wherein said amplifying comprises carrying out polymerase chain reaction. 63. The method of claim 54, comprising contacting said sample with a nucleic acid molecule which specifically hybridizes to a nucleic acid molecule which codes for or expresses said SCP protein. 64. The method of claim 54, comprising assaying said sample for said peptide.

Inventors: PFREUNDSCHUH MICHAEL, SAHIN UGUR, TURECI OZLEM, PFREUNDSCHUH, MICHAEL, SAHIN, UGUR, TURECI, OZLEM
Applicants: LUDWIG INST CANCER RES, LUDWIG INSTITUTE FOR CANCER RESEARCH
Application year: 1998
Main classification: C12Q1
IPC codes: A61K31, A61K35, A61K38, A61K39, A61K45, A61K48, A61P35, A61P43, C07H21, C07K14, C07K16, C12N15, C12P21, C12Q1, G01N33