Patent Abstract:
compositions and methods to treat lymphoma and cancer are disclosed . in particular , the method teaches treatment of lymphoma and cancer using anti - herv - k therapies . further taught are compositions and methods for characterizing patient samples to , for example , select or identify therapeutic options or assess the impact of therapies .

Detailed Description:
the present invention provides methods to treat and diagnose lymphoma and cancer . in particular , the present invention provides treatment of lymphoma and cancer using anti - herv - k ( hml - 2 ) therapies . accordingly , the present invention provides methods , reagents , and kits for the detection of markers , drug screening , and therapeutic applications . in some embodiments , herv - k ( hml - 2 ) is a cancer marker ( e . g . marker of lymphoma ). in some embodiments , herv - k ( hml - 2 ) is a cancer causative agent . the practice of the present invention will employ , unless indicated specifically to the contrary , conventional methods of virology , immunology , microbiology , molecular biology and recombinant dna techniques within the skill of the art , many of which are described below for the purpose of illustration . such techniques are explained fully in the literature . see , e . g ., sambrook , et al . molecular cloning : a laboratory manual ( 2nd edition , 1989 ); maniatis et al . molecular cloning : a laboratory manual ( 1982 ); dna cloning : a practical approach , vol . i & amp ; ii ( d . glover , ed . ); oligonucleotide synthesis ( n . gait , ed ., 1984 ); nucleic acid hybridization ( b . flames & amp ; s . higgins , eds ., 1985 ); transcription and translation ( b . hames & amp ; s . higgins , eds ., 1984 ); animal cell culture ( r . freshney , ed ., 1986 ); perbal , a practical guide to molecular cloning ( 1984 ). the human genome harbors numerous retroviral sequences that comprise up to 8 % of the host genome , many of which have accumulated lethal mutations that have impaired their ability to replicate . ( nelson et al . mol pathol 2003 ; 56 : 11 - 18 ; wang - johanning et al . oncogene 2003 ; 22 : 1528 - 1535 ; hughes et al . proc natl acad sci usa 2004 ; 101 : 1688 - 1672 ). the human endogenous retrovirus type - k ( herv - k . hml - 2 ) family is represented by many proviruses , some of which possess intact open reading frames ( orfs ) for gag , prt , pol , and env genes . ( barbulescu et al . curr biol 1999 ; 9 : 861 - 868 ; paces et al . nucleic acids res 2002 ; 30 : 205 - 206 ). herv - k ( hml - 2 ) is an endogenous retroviral subfamily with the ability to produce viral particles . ( bannert et al . proc natl acad sci usa 2002 ; 101 suppl 2 : 14572 - 14579 ; simpson et al . virology 1996 ; 222 : 451 - 456 ; bieda et al . j gen virol 2001 ; 3 : 591 - 596 ; boller et al . virology 1993 ; 1 : 349 - 353 ). however , an intact herv - k proviral sequence ( k113 ) and perhaps other unidentified unfixed elements may code for replication - competent viruses . ( turner et al . curr biol 2001 ; 11 : 1531 - 1535 ; moyes et al . genomics 2005 ; 86 : 337 - 341 ; bleshaw et al . j virol 2005 ; 79 : 12507 - 12514 ). the detection of anti - herv - k antibodies in the plasma of 70 % of hiv - 1 patients compared to only 3 % of healthy blood donors . ( lower et al . proc natl acad sci usa 1996 ; 93 : 5177 - 5184 ). antibodies to herv - k were also detectable in drug users , but only after hiv - 1 seroconversion . ( vogetseder et al . aids res hum retroviruses 1993 ; 9 : 687 - 694 ). u . s . patent application 20080261216 , herein incorporated by reference in its entirety , describes that it was found that if herv - k viral particles are made , they may be protected by viral envelopes in plasma of hiv - 1 infected individuals , and that the rna genome is directly amplified from viral rna extractions of plasma . all of the above references are herein incorporated by reference in their entireties . in some embodiments , the present invention provides therapies for cancer and cancer - related illnesses ( e . g . acute lymphoblastic leukemia , acute myeloid leukemia , adrenocortical carcinoma , aids - related cancers , aids - related lymphoma , anal cancer , appendix cancer , astrocytoma , atypical teratoid / rhabdoid tumor , basal cell carcinoma , bile duct cancer , bladder cancer , bone cancer ( e . g . osteosarcoma or malignant fibrous histiocytoma ), brain stem glioma , brain tumor ( e . g . adult , childhood , brain stem glioma , atypical teratoid / rhabdoid tumor , embryonal tumors , cerebellar astrocytoma , cerebral astrocytoma , malignant glioma , craniopharyngioma , ependymoblastoma , ependymoma , medulloblastoma , medulloepithelioma , pineal parenchymal tumors of intermediate differentiation , supratentorial primitive neuroectodermal tumors and pineoblastoma , visual pathway and hypothalamic glioma , brain and spinal cord tumors ), breast cancer , bronchial tumors , burkitt lymphoma , carcinoid tumor , carcinoma , atypical teratoid / rhabdoid tumor , embryonal tumors , central nervous system lymphoma , cerebellar astrocytoma , cervical cancer , childhood cancers , chordoma , chronic lymphocytic leukemia , chronic myelogenous leukemia , chronic myeloproliferative disorders , colon cancer , colorectal cancer , craniopharyngioma , cutaneous t - cell lymphoma , embryonal tumors , endometrial cancer , ependymoblastoma , ependymoma , esophageal cancer , ewing family of tumors , extracranial germ cell tumor , extragonadal germ cell tumor , extrahepatic bile duct cancer , eye cancer ( e . g . intraocular melanoma , retinoblastoma , etc . ), gallbladder cancer , gastric ( stomach ) cancer , gastrointestinal carcinoid tumor , gastrointestinal stromal tumor ( gist ), germ cell tumor ( e . g . extracranial , extragonadal , ovarian , etc . ), gestational trophoblastic tumor , glioma ( e . g ., adult , childhood , brain stem , cerebral astrocytoma , visual pathway and hypothalamic , etc . ), hairy cell leukemia , head and neck cancer , hepatocellular ( liver ) cancer , hodgkin lymphoma , hypopharyngeal cancer , hypothalamic and visual pathway glioma , intraocular melanoma , islet cell tumors ( endocrine pancreas ), kaposi sarcoma , kidney ( renal cell ) cancer , laryngeal cancer , leukemia ( e . g . acute , lymphoblastic , adult , childhood , acute myeloid , chronic lymphocytic , chronic myelogenous , hairy cell , etc . ), lip and oral cavity cancer , liver cancer , lung cancer ( e . g . non - small cell , small cell , etc . ), lymphoma ( e . g . aids - related , burkitt , cutaneous t - cell , mycosis fungoides , sézary syndrome , hodgkin , adult , childhood , non - hodgkin , primary central nervous system , etc . ), macroglobulinemia , malignant fibrous histiocytoma of bone and osteosarcoma , medulloblastoma , medulloepithelioma , melanoma , merkel cell carcinoma , mesothelioma , metastatic squamous neck cancer , mouth cancer , multiple endocrine neoplasia syndrome , multiple myeloma / plasma cell neoplasm , mycosis fungoides , myelodysplastic syndromes , myelodysplastic / myeloproliferative diseases , myelogenous leukemia ( e . g . chronic , acute , etc . ), myeloid leukemia , myeloma , myeloproliferative disorders , nasal cavity and paranasal sinus cancer , nasopharyngeal cancer , neuroblastoma , oral cancer , oropharyngeal cancer , osteosarcoma and malignant fibrous histiocytoma of bone , ovarian cancer ( e . g . childhood , ovarian epithelial cancer , ovarian germ cell tumor , ovarian low malignant potential tumor , etc . ), pancreatic cancer , islet cell tumors , papillomatosis , paranasal sinus and nasal cavity cancer , parathyroid cancer , penile cancer , pharyngeal cancer , pheochromocytoma , pineal parenchymal tumors of intermediate differentiation , pineoblastoma and supratentorial primitive neuroectodermal tumors , pituitary tumor , plasma cell neoplasm / multiple myeloma , pleuropulmonary blastoma , pregnancy and breast cancer , primary central nervous system lymphoma , prostate cancer , rectal cancer , renal cell ( kidney ) cancer , renal pelvis and ureter , respiratory tract carcinoma involving the nut gene on chromosome 15 , retinoblastoma , rhabdomyosarcoma , salivary gland cancer sarcoma , ( e . g . ewing family of tumors , kaposi , soft tissue , adult , childhood , uterine , etc . ), sézary syndrome , skin cancer ( e . g . nonmelanoma , childhood , melanoma , carcinoma , merkel cell , etc .) small intestine cancer , soft tissue sarcoma , squamous cell carcinoma , squamous neck cancer with occult primary , stomach ( gastric ) cancer , supratentorial primitive neuroectodermal tumors , t - cell lymphoma , testicular cancer , throat cancer , thymoma and thymic carcinoma , thyroid cancer , transitional cell cancer of the renal pelvis and ureter , trophoblastic tumor , unknown primary site , unusual cancers of childhood ureter and renal pelvis , urethral cancer , uterine cancer ( e . g . endometrial , uterine sarcoma , etc . ), vaginal cancer , visual pathway and hypothalamic glioma , vulvar cancer , waldenström macroglobulinemia , wilms tumor , etc .). in some embodiments of the present invention , pharmaceutical compositions are used for the treatment of cancer . in some embodiments of the present invention , pharmaceutical compositions are used for the treatment of viral infection ( e . g . herv - k ( hml - 2 )). in some embodiments of the present invention , pharmaceutical compositions are used for the treatment of cancer by the reduction of retroviral load ( e . g . herv - k ( hml - 2 )). within such methods , the pharmaceutical compositions described herein are administered to a patient , typically a warm - blooded animal ( e . g . a human ). a patient may or may not be afflicted with cancer . accordingly , the above pharmaceutical compositions may be used to prevent the development of a cancer or to treat a patient afflicted with a cancer . a patient may or may not have circulating viral particles ( e . g . herv - k ( hml - 2 ) particles ). accordingly , the above pharmaceutical compositions may be used to prevent the spread or production of a viral particles ( e . g . herv - k ( hml - 2 )) or to treat a patient afflicted with viral particles ( e . g . herv - k ( hml - 2 )). in some embodiments , a patient treated by the present invention is not infected with hiv ( e . g . hiv - 1 , hiv - 2 , etc .). pharmaceutical compositions and vaccines may be administered either prior to or following surgical removal of primary tumors and / or treatment such as administration of radiotherapy or conventional chemotherapeutic drugs . as discussed herein , administration of the pharmaceutical compositions may be by any suitable method , including administration by intravenous , intraperitoneal , intramuscular , subcutaneous , intranasal , intradermal , anal , vaginal , topical and oral routes . in some embodiments , the present invention provides therapies that kill cancer cells , induce apoptosis in cancer cells , stop or slow the spread of cancer , stop or reduce cancer metastasis , stop or reduce tumor formation , reduce tumor load , minimize the effects of cancer , support the ability of the body to fight cancer , and / or serve as an antagonist to cancer , cancer cells , or cancer - related diseases . in some embodiments , the compounds act as a cancer therapy by directly or indirectly targeting a cancer marker ( e . g . herv - k ( hml - 2 )). in some embodiments , the present invention provides methods , regents , and kits that are cancer therapies . in some embodiments , the present invention treats cancer ( e . g . lymphoma ) by reducing or eliminating the viral load ( e . g . one of more retroviruses ( e . g . herv - k ( hml - 2 ))) within a subject . in some embodiments , one or more retroviruses and / or retroviral elements ( e . g . herv - k ( hml - 2 )) are a cause of , the cause of , a contributing factor to , and / or an aggravating factor to cancer ( e . g . breast cancer , lymphoma , etc .) and / or cancer - related illnesses . in some embodiments , reducing the viral load of herv - k ( hml - 2 ) and / or other retroviruses provides a cancer therapy ( e . g . killing cancer cells , reducing tumor load , etc .). in some embodiments , herv - k ( hml - 2 ) viral proteins are expressed from exogenous genes ( e . g . genes which have infected a subject ). in some embodiments , herv - k ( hml - 2 ) viral proteins are expressed from endogenous genes ( e . g . viral protein genes which are integrated into the subject &# 39 ; s genome ). in some embodiments , herv - k ( hml - 2 ) viral proteins expressed within a subject are capable of assembling into a viral element ( e . g . virion , virus , mature virus , viral particle , etc .). in some embodiments , viral elements ( e . g . virion , virus , mature virus , viral particle , etc .) produced and assembled within a subject are capable of reinfecting the subject , infecting another subject , reproducing , and / or replicating . in some embodiments , herv - k ( hml - 2 ) viral proteins expressed within a subject are not capable of assembling into a viral element ( e . g . virion , virus , mature virus , viral particle , etc .). in some embodiments , viral elements ( e . g . virion , virus , mature virus , viral particle , etc .) produced and assembled within a subject are not capable of reinfecting the subject , infecting another subject , reproducing , and / or replicating . in some embodiments , viral proteins ( e . g . herv - k ( hml - 2 ) viral proteins ) are expressed from one or more endogenous genes within a subject &# 39 ; s genome . in some embodiments , the present invention provides one or more antiviral therapies . in some embodiments , compounds of the present invention inhibit one or more retroviruses or retroviral elements ( e . g . hiv - 1 , hiv - 2 , herv - k ( hml - 2 , etc .). as one skilled in the art will appreciate , the compounds of the present invention may inhibit a variety of retroviruses , retroviral elements , and may inhibit viruses , other than retroviruses . compounds which inhibit one or more of the following may also find utility in the present invention : herv - k ( hml - 2 ) type 1 , herv - k ( hml - 2 ) type 2 , type c and type d retroviruses , htlv - 1 , htlv - 2 , hiv , flv , siv , mlv , blv , biv , equine infections , anemia virus , avian sarcoma viruses , such as rous sarcoma virus ( rsv ), hepatitis type a , b , non - a and non - b viruses , arboviruses , varicella viruses , measles , mumps , rubella viruses , etc . in some embodiments , the present invention provides antiviral therapies in doses and / or combinations which are not useful ( or are sub - optimally useful ) as therapies against hiv ( e . g . removal of a pharmaceutical form a combinatorial therapy ( e . g . removal of a fusion inhibitor from a multi - drug antiviral therapy , or removal of a protease from a multi - drug antiviral therapy ), replacement of a pharmaceutical in a combinatorial therapy , or a dose which would be ineffective or not commonly used in treating hiv ). in some embodiments , the present invention provides antiviral therapies in doses and / or combinations which are not preferred as a therapy against hiv . in some embodiments , the treatment regimens of the present invention differ from the most effective hiv treatment regimens ( robbins et al . 2003 , n engl j med , 349 ; 24 , shafer et al . 2003 , n engl j med , 349 ; 24 , herein incorporated by reference in their entireties ) in one or more ways ( e . g . dose , combination of drugs , etc .). in some embodiments , treatments of the present invention find utility in treating hiv - infected subject and / or non - hiv - infected subjects . in some embodiments , the present invention provides antiretroviral drugs comprising one or more of , but not limited to , reverse transcriptase inhibitors , nucleoside analog reverse transcriptase inhibitors ( e . g . zidovudine , didanosine , zalcitabine , stavudine , lamivudine , abacavir , emtricitabine , atricitabine , etc . ), nucleotide analog reverse transcriptase inhibitors ( e . g . tenofovir , adefovir , etc . ), non - nucleoside reverse transcriptase inhibitors ( e . g . efavirenz , nevirapine , delavirdine , etravirine , etc . ), protease inhibitors ( e . g . saquinavir , ritonavir , indinavir , nelfinavir , amprenavir , lopinavir , atazanavir , fosamprenavir , tipranavir , darunavir , etc . ), fusion inhibitors ( e . g . maraviroc , enfuvirtide , etc . ), integrase inhibitors ( e . g . raltegravir , elitegravir , etc . ), entry inhibitors ( e . g . maraviroc , enfuvirtide , etc . ), maturation inhibitors ( e . g . bevirimat , etc . ), portmanteau inhibitors , etc . in some embodiments , the present invention provides any compounds that function as an antiretroviral ( e . g . azt ( zidovudine ), ftc ( emtricitabine ), 3tc ( lamivudine ), ddc ( zalcitabine ), d4t ( stavudine ), ddi ( dideoxyinosine ), tdf ( tenofovir disoproxyl fumarato ), abc ( abacavir ), β - d hydroxy cytidine , efavirenz , nevirapine , etravirine , atazanavir , ritonavir , indinavir , amprenavir , etc .). in some embodiments , the present invention provides antiretroviral therapies that include administration of one or more pharmaceutical compounds ( e . g . 1 compound , 2 compounds , 3 compounds , 4 compounds , 5 compounds , 6 compounds , 7 compounds , 8 compounds , 9 compounds , 10 compounds , & gt ; 10 compounds ). in some embodiments , the present invention provides combination therapy in which two or more compounds are simultaneously administered or administered in sequence . in some embodiments , the present invention provides highly active antiretroviral therapy ( haart ) or the administration of a plurality of different antiretroviral drugs in combination to overwhelm the ability of a retrovirus to develop resistance to a single therapy : in some embodiments , the present invention provides a regimen involving administration of one or more approaches including but not limited to antiretrovirals , cancer chemotherapy , radiation , diet , exercise , surgery , nutrition , supplementation , etc . in some embodiments , one or more antiretroviral therapies ( e . g . one or more pharmaceuticals ) are administered in combination with one or more cancer therapies ( e . g . chemotherapy , radiation , etc .). in some embodiments , the present invention provides drug screening assays ( e . g ., to screen for anticancer drugs ). the screening methods of the present invention utilize cancer markers identified using the methods of the present invention ( e . g ., including but not limited to , herv - k ( hml - 2 ) targets ). for example , in some embodiments , the present invention provides methods of screening for compounds that alter ( e . g ., decrease ) the production of cancer markers . the compounds or agents may interfere with transcription . the compounds or agents may interfere with mrna produced from : herv - k ( hml - 2 ) ( e . g ., by rna interference , antisense technologies , etc .). the compounds or agents may interfere with pathways that are upstream or downstream of the biological activity of the herv - k ( hml - 2 ) target . in some embodiments , candidate compounds are antisense or interfering rna agents ( e . g ., oligonucleotides ) directed against cancer markers ( e . g . herv - k ( hml - 2 ). in some embodiments , compounds or agents may interfere with herv - k ( hml - 2 ) replication . in other embodiments , candidate compounds are antibodies or small molecules that specifically bind to a cancer marker regulators or expression products of the present invention and inhibit its biological function . in one screening method , candidate compounds are evaluated for their ability to alter cancer marker production by contacting a compound with a cell producing a cancer marker and then assaying for the effect of the candidate compounds on expression . in some embodiments , the effect of candidate compounds on production of a cancer marker is assayed for by detecting the level of cancer marker mrna expressed by the cell . mrna expression can be detected by any suitable method . in other embodiments , the effect of candidate compounds on expression of cancer marker genes is assayed by measuring the level of polypeptide encoded by the cancer markers . the level of polypeptide expressed can be measured using any suitable method , including but not limited to , those disclosed herein . specifically , the present invention provides screening methods for identifying modulators , i . e ., candidate or test compounds or agents ( e . g ., proteins , peptides , peptidomimetics , peptoids , small molecules or other drugs ) which bind to cancer markers of the present invention , have an inhibitory ( or stimulatory ) effect on , for example , cancer marker production or cancer marker activity , or have a stimulatory or inhibitory effect on , for example , the expression or activity of a cancer marker substrate . compounds thus identified can be used to modulate the activity of target gene products ( e . g ., cancer marker genes ( e . g . ( e . g ., herv - k ( hml - 2 ) gene or genes )) either directly or indirectly in a therapeutic protocol , to elaborate the biological function of the target gene product , or to identify compounds that disrupt normal target gene interactions . compounds that inhibit the activity or expression of cancer markers are useful in the treatment of proliferative disorders , e . g ., cancer , particularly lymphoma , leukemia and breast cancer . in one embodiment , the invention provides assays for screening candidate or test compounds that are substrates of a cancer marker protein or polypeptide or a biologically active portion thereof ( e . g ., herv - k ( hml - 2 ) proteins ). in another embodiment , the invention provides assays for screening candidate or test compounds that bind to or modulate the activity of a cancer marker protein or polypeptide or a biologically active portion thereof ( e . g ., herv - k ( hml - 2 ) proteins ). in some embodiments , the invention provides assays for screening candidate or test compounds that are inhibitors of viral replication ( e . g . retroviral replication ( e . g . herv - k ( hml - 2 ) replication )). in another embodiment , the invention provides assays for screening candidate or test compounds that bind to or modulate the effects of viruses ( e . g . retroviruses ( e . g . herv - k ( hml - 2 ))), spread of viruses , expression of viral proteins , etc . the test compounds of the present invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art , including biological libraries ; peptoid libraries ( libraries of molecules having the functionalities of peptides , but with a novel , non - peptide backbone , which are resistant to enzymatic degradation but which nevertheless remain bioactive ; see , e . g ., zuckennann et al ., j . med . chem . 37 : 2678 - 85 [ 1994 ]); spatially addressable parallel solid phase or solution phase libraries ; synthetic library methods requiring deconvolution ; the one - bead one - compound library method ; and synthetic library methods using affinity chromatography selection . the biological library and peptoid library approaches are preferred for use with peptide libraries , while the other four approaches are applicable to peptide , non - peptide oligomer or small molecule libraries of compounds ( lam ( 1997 ) anticancer drug des . 12 : 145 ). examples of methods for the synthesis of molecular libraries can be found in the art , for example in : dewitt et al ., proc . natl . acad . sci . u . s . a . 90 : 6909 [ 1993 ]; erb et al ., proc . nad . acad . sci . usa 91 : 11422 [ 1994 ]; zuckermann et al ., j . med . chem . 37 : 2678 [ 1994 ]; cho et al ., science 261 : 1303 [ 1993 ]; carrell et al ., angew . chem . int . ed . engl . 33 . 2059 [ 1994 ]; carell et al ., angew . chem . int . ed . engl . 33 : 2061 [ 1994 ]; and gallop et al ., j . med . chem . 37 : 1233 [ 1994 ]. libraries of compounds may be presented in solution ( e . g ., houghten , biotechniques 13 : 412 - 421 [ 1992 ]), or on beads ( lam , nature 354 : 82 - 84 [ 1991 ]), chips ( fodor , nature 364 : 555 - 556 [ 1993 ]), bacteria or spores ( u . s . pat . no . 5 , 223 , 409 ; herein incorporated by reference ), plasmids ( cull et al ., proc . nad . acad . sci . usa 89 : 18651869 [ 1992 ]) or on phage ( scott and smith , science 249 : 386 - 390 [ 1990 ]; devlin science 249 : 404 - 406 [ 1990 ]; cwirla et al ., proc . natl . acad . sci . 87 : 6378 - 6382 [ 1990 ]; felici , j . mol . biol . 222 : 301 [ 1991 ]). in some embodiments , an assay is a cell - based assay in which a cell that expresses a cancer marker mrna or protein , a biologically active portion thereof , or a viral particle cancer marker ( e . g . herv - k ( hml - 2 )) is contacted with a test compound , and the ability of the test compound to the modulate cancer marker &# 39 ; s activity is determined . determining the ability of the test compound to modulate cancer marker activity can be accomplished by monitoring , for example , changes in enzymatic activity , destruction or mrna , viral load , or the like . the ability of the test compound to modulate cancer marker binding to a compound , e . g ., a cancer marker substrate or modulator , can also be evaluated . this can be accomplished , for example , by coupling the compound , e . g ., the substrate , with a radioisotope or enzymatic label such that binding of the compound , e . g ., the substrate , to a cancer marker can be determined by detecting the labeled compound , e . g ., substrate , in a complex . this invention further pertains to novel agents identified by the above - described screening assays ( see e . g ., below description of cancer therapies ). accordingly , it is within the scope of this invention to further use an agent identified as described herein ( e . g ., a cancer marker modulating agent , an antisense cancer marker nucleic acid molecule , a sirna molecule , a cancer marker specific antibody , or a cancer marker - binding partner ) in an appropriate animal model ( such as those described herein ) to determine the efficacy , toxicity , side effects , or mechanism of action , of treatment with such an agent . furthermore , novel agents identified by the above - described screening assays can be , e . g ., used for treatments as described herein . in some embodiments , the present invention provides therapies for cancer ( e . g ., lymphoma , leukemia or breast cancer ). in some embodiments , therapies directly or indirectly target cancer markers ( e . g ., herv - k ( hml - 2 ) target ). in some embodiments , the present invention targets the production of cancer markers ( e . g ., herv - k ( hml - 2 ). for example , in some embodiments , the present invention employs compositions comprising oligomeric antisense or rnai compounds , particularly oligonucleotides ( e . g ., those identified in the drug screening methods described above ), for use in modulating the function of nucleic acid molecules encoding cancer markers of the present invention ( e . g ., herv - k ( hml - 2 ), ultimately modulating the amount of cancer marker expressed . in some embodiments , rnai is utilized to inhibit herv - k ( hml - 2 ) target function . rnai represents an evolutionary conserved cellular defense for controlling the expression of foreign genes in most eukaryotes , including humans . rnai is typically triggered by double - stranded rna ( dsrna ) and causes sequence - specific mrna degradation of single - stranded target rnas homologous in response to dsrna . the mediators of mrna degradation are small interfering rna duplexes ( sirnas ), which are normally produced from long dsrna by enzymatic cleavage in the cell . sirnas are generally approximately twenty - one nucleotides in length ( e . g ., 21 - 23 nucleotides in length ), and have a base - paired structure characterized by two nucleotide 3 ′- overhangs . following the introduction of a small rna , or rnai , into the cell , it is believed the sequence is delivered to an enzyme complex called risc ( rna - induced silencing complex ). risc recognizes the target and cleaves it with an endonuclease . it is noted that if larger rna sequences are delivered to a cell , rnase iii enzyme ( dicer ) converts longer dsrna into 21 - 23 nt ds sirna fragments . in some embodiments , rnai oligonucleotides are designed to target the herv - k ( hml - 2 ) proteins . chemically synthesized sirnas have become powerful reagents for genome - wide analysis of mammalian gene function in cultured somatic cells . beyond their value for validation of gene function , sirnas also hold great potential as gene - specific therapeutic agents ( tuschl and borkhardt , molecular intervent . 2002 ; 2 ( 3 ): 158 - 67 , herein incorporated by reference ). the transfection of sirnas into animal cells results in the potent , long - lasting post - transcriptional silencing of specific genes ( caplen et al , proc natl acad sci u . s . a . 2001 ; 98 : 9742 - 7 ; elbashir et al ., nature . 2001 ; 411 : 494 - 8 ; elbashir et al ., genes dev . 2001 ; 15 : 188 - 200 ; and elbashir et al ., embo j . 2001 ; 20 : 6877 - 88 , all of which are herein incorporated by reference ). methods and compositions for performing rnai with sirnas are described , for example , in u . s . pat . no . 6 , 506 , 559 , herein incorporated by reference . sirnas are extraordinarily effective at lowering the amounts of targeted rna , and by extension proteins , frequently to undetectable levels . the silencing effect can last several months , and is extraordinarily specific , because one nucleotide mismatch between the target rna and the central region of the sirna is frequently sufficient to prevent silencing ( brummelkamp et al , science 2002 ; 296 : 550 - 3 ; and holen et al , nucleic acids res . 2002 ; 30 : 1757 - 66 , both of which are herein incorporated by reference ). an important factor in the design of sirnas is the presence of accessible sites for sirna binding . bahoia et al ., ( j . biol . chem ., 2003 ; 278 : 15991 - 15997 ; herein incorporated by reference ) describe the use of a type of dna array called a scanning array to find accessible sites in mrnas for designing effective sirnas . these arrays comprise oligonucleotides ranging in size from monomers to a certain maximum , usually synthesized using a physical barrier ( mask ) by stepwise addition of each base in the sequence . thus the arrays represent a full oligonucleotide complement of a region of the target gene . hybridisation of the target mrna to these arrays provides an exhaustive accessibility profile of this region of the target mrna . such data are useful in the design of antisense oligonucleotides ( ranging from 7 mers to 25 mers ), where it is important to achieve a compromise between oligonucleotide length and binding affinity , to retain efficacy and target specificity ( sohail et al , nucleic acids res ., 2001 ; 29 ( 10 ): 2041 - 2045 ). additional methods and concerns for selecting sirnas are described for example , in wo 05054270 , wo05038054a1 , wo03070966a2 , j . mol . biol . 2005 may 13 ; 348 ( 4 ): 883 - 93 , j . mol . biol . 2005 may 13 ; 348 ( 4 ): 871 - 81 , and nucleic acids res . 2003 aug . 1 ; 31 ( 15 ): 4417 - 24 , each of which is herein incorporated by reference in its entirety . in addition , software ( e . g ., the mwg online simax sirna design tool ) is commercially or publicly available for use in the selection of sirnas . in some embodiments , herv - k ( hml - 2 ) protein expression is modulated using antisense compounds that specifically hybridize with one or more nucleic acids encoding cancer markers of the present invention . the specific hybridization of an oligomeric compound with its target nucleic acid interferes with the normal function of the nucleic acid . this modulation of function of a target nucleic acid by compounds that specifically hybridize to it is generally referred to as “ antisense .” the functions of dna to be interfered with include replication and transcription . the functions of rna to be interfered with include all vital functions such as , for example , translocation of the rna to the site of protein translation , translation of protein from the rna , splicing of the rna to yield one or more mrna species , and catalytic activity that may be engaged in or facilitated by the rna . the overall effect of such interference with target nucleic acid function is modulation of the expression of cancer markers of the present invention . in the context of the present invention , “ modulation ” means either an increase ( stimulation ) or a decrease ( inhibition ) in the expression of a gene . for example , expression may be inhibited to potentially prevent tumor proliferation . in some embodiments , specific nucleic acids are targeted for antisense . “ targeting ” an antisense compound to a particular nucleic acid , in the context of the present invention , is a multi - step process . the process usually begins with the identification of a nucleic acid sequence whose function is to be modulated . this may be , for example , a cellular gene ( or mrna transcribed from the gene ) whose expression is associated with a particular disorder or disease state , or a nucleic acid molecule from an infectious agent . in the present invention , the target is a nucleic acid molecule encoding a cancer marker of the present invention . the targeting process also includes determination of a site or sites within this gene for the antisense interaction to occur such that the desired effect , e . g ., detection or modulation of expression of the protein , will result . within the context of the present invention , a preferred intragenic site is the region encompassing the translation initiation or termination codon of the open reading frame ( orf ) of the gene . since the translation initiation codon is typically 5 ′- aug ( in transcribed mrna molecules ; 5 ′- atg in the corresponding dna molecule ), the translation initiation codon is also referred to as the “ aug codon ,” the “ start codon ” or the “ aug start codon ”. a few genes have a translation initiation codon having the rna sequence 5 ′- gug , 5 ′- uug or 5 ′- cug , and 5 ′- aua , 5 ′- acg and 5 ′- cug have been shown to function in vivo . thus , the terms “ translation initiation codon ” and “ start codon ” can encompass many codon sequences , even though the initiator amino acid in each instance is typically methionine ( in eukaryotes ) or formylmethionine ( in prokaryotes ). eukaryotic and prokaryotic genes may have two or more alternative start codons , any one of which may be preferentially utilized for translation initiation in a particular cell type or tissue , or under a particular set of conditions . in the context of the present invention , “ start codon ” and “ translation initiation codon ” refer to the codon or codons that are used in vivo to initiate translation of an mrna molecule transcribed from a gene encoding a tumor antigen of the present invention , regardless of the sequence ( s ) of such codons . translation termination codon ( or “ stop codon ”) of a gene may have one of three sequences ( i . e ., 5 ′- uaa , 5 ′- uag and 5 ′- uga ; the corresponding dna sequences are 5 ′- taa , 5 ′- tag and 5 ′- tga , respectively ). the terms “ start codon region ” and “ translation initiation codon region ” refer to a portion of such an mrna or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction ( i . e ., 5 ′ or 3 ′) from a translation initiation codon . similarly , the terms “ stop codon region ” and “ translation termination codon region ” refer to a portion of such an mrna or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction ( i . e ., 5 ′ or 3 ′) from a translation termination codon . the open reading frame ( orf ) or “ coding region ,” which refers to the region between the translation initiation codon and the translation termination codon , is also a region that may be targeted effectively . other target regions include the 5 ′ untranslated region ( 5 ′ utr ), referring to the portion of an mrna in the 5 ′ direction from the translation initiation codon , and thus including nucleotides between the 5 ′ cap site and the translation initiation codon of an mrna or corresponding nucleotides on the gene , and the 3 ′ untranslated region ( 3 ′ utr ), referring to the portion of an mrna in the 3 ′ direction from the translation termination codon , and thus including nucleotides between the translation termination codon and 3 ′ end of an mrna or corresponding nucleotides on the gene . the 5 ′ cap of an mrna comprises an n7 - methylated guanosine residue joined to the 5 ′- most residue of the mrna via a 5 ′- 5 ′ triphosphate linkage . the 5 ′ cap region of an mrna is considered to include the 5 ′ cap structure itself as well as the first 50 nucleotides adjacent to the cap . the cap region may also be a preferred target region . although some eukaryotic mrna transcripts are directly translated , many contain one or more regions , known as “ introns ,” that are excised from a transcript before it is translated . the remaining ( and therefore translated ) regions are known as “ exons ” and are spliced together to form a continuous mrna sequence . mrna splice sites ( i . e ., intron - exon junctions ) may also be preferred target regions , and are particularly useful in situations where aberrant splicing is implicated in disease , or where an overproduction of a particular mrna splice product is implicated in disease . it has also been found that introns can also be effective , and therefore preferred , target regions for antisense compounds targeted , for example , to dna or pre - mrna . in some embodiments , target sites for antisense inhibition are identified using commercially available software programs ( e . g ., biognostik , gottingen , germany ; sysarris software , bangalore , india ; antisense research group , university of liverpool , liverpool , england ; genetrove , carlsbad , calif .). in other embodiments , target sites for antisense inhibition are identified using the accessible site method described in u . s . patent wo0198537a2 , herein incorporated by reference . once one or more target sites have been identified , oligonucleotides are chosen that are sufficiently complementary to the target ( i . e ., hybridize sufficiently well and with sufficient specificity ) to give the desired effect . for example , in preferred embodiments of the present invention , antisense oligonucleotides are targeted to or near the start codon . in the context of this invention , “ hybridization ,” with respect to antisense compositions and methods , means hydrogen bonding , which may be watson - crick , hoogsteen or reversed hoogsteen hydrogen bonding , between complementary nucleoside or nucleotide bases . for example , adenine and thymine are complementary nucleobases that pair through the formation of hydrogen bonds . it is understood that the sequence of an antisense compound need not be 100 % complementary to that of its target nucleic acid to be specifically hybridizable . an antisense compound is specifically hybridizable when binding of the compound to the target dna or rna molecule interferes with the normal function of the target dna or rna to cause a loss of utility , and there is a sufficient degree of complementarity to avoid non - specific binding of the antisense compound to non - target sequences under conditions in which specific binding is desired ( i . e ., under physiological conditions in the case of in vivo assays or therapeutic treatment , and in the case of in vitro assays , under conditions in which the assays are performed ). antisense compounds are commonly used as research reagents and diagnostics . for example , antisense oligonucleotides , which are able to inhibit gene expression with specificity , can be used to elucidate the function of particular genes . antisense compounds are also used , for example , to distinguish between functions of various members of a biological pathway . the specificity and sensitivity of antisense is also applied for therapeutic uses . for example , antisense oligonucleotides have been employed as therapeutic moieties in the treatment of disease states in animals and man . antisense oligonucleotides have been safely and effectively administered to humans and numerous clinical trials are presently underway . it is thus established that oligonucleotides are useful therapeutic modalities that can be configured to be useful in treatment regimes for treatment of cells , tissues , and animals , especially humans . while antisense oligonucleotides are a preferred form of antisense compound , the present invention comprehends other oligomeric antisense compounds , including but not limited to oligonucleotide mimetics such as are described below . the antisense compounds in accordance with this invention preferably comprise from about 8 to about 30 nucleobases ( i . e ., from about 8 to about 30 linked bases ), although both longer and shorter sequences may find use with the present invention . particularly preferred antisense compounds are antisense oligonucleotides , even more preferably those comprising from about 12 to about 25 nucleobases . specific examples of preferred antisense compounds useful with the present invention include oligonucleotides containing modified backbones or non - natural internucleoside linkages . as defined in this specification , oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone . for the purposes of this specification , modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides . preferred modified oligonucleotide backbones include , for example , phosphorothioates , chiral phosphorothioates , phosphorodithioates , phosphotriesters , aminoalkylphosphotriesters , methyl and other alkyl phosphonates including 3 ′- alkylene phosphonates and chiral phosphonates , phosphinates , phosphoramidates including 3 ′- amino phosphoramidate and aminoalkylphosphoramidates , thionophosphoramidates , thionoalkylphosphonates , thionoalkylphosphotriesters , and boranophosphates having normal 3 ′- 5 ′ linkages , 2 ′- 5 ′ linked analogs of these , and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3 ′- 5 ′ to 5 ′- 3 ′ or 2 ′- 5 ′ to 5 ′- 2 ′. various salts , mixed salts and free acid forms are also included . preferred modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages , mixed heteroatom and alkyl or cycloalkyl internucleoside linkages , or one or more short chain heteroatomic or heterocyclic internucleoside linkages . these include those having morpholino linkages ( formed in part from the sugar portion of a nucleoside ); siloxane backbones ; sulfide , sulfoxide and sulfone backbones ; formacetyl and thioformacetyl backbones ; methylene formacetyl and thioformacetyl backbones ; alkene containing backbones ; sulfamate backbones ; methyleneimino and methylenehydrazino backbones ; sulfonate and sulfonamide backbones ; amide backbones ; and others having mixed n , o , s and ch 2 component parts . in other preferred oligonucleotide mimetics , both the sugar and the internucleoside linkage ( i . e ., the backbone ) of the nucleotide units are replaced with novel groups . the base units are maintained for hybridization with an appropriate nucleic acid target compound . one such oligomeric compound , an oligonucleotide mimetic that has been shown to have excellent hybridization properties , is referred to as a peptide nucleic acid ( pna ). in pna compounds , the sugar - backbone of an oligonucleotide is replaced with an amide containing backbone , in particular an aminoethylglycine backbone . the nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone . representative united states patents that teach the preparation of pna compounds include , but are not limited to , u . s . pat . nos . 5 , 539 , 082 ; 5 , 714 , 331 ; and 5 , 719 , 262 , each of which is herein incorporated by reference . further teaching of pna compounds can be found in nielsen et al ., science 254 : 1497 ( 1991 ). most preferred embodiments of the invention are oligonucleotides with phosphorothioate backbones and oligonucleosides with heteroatom backbones , and in particular — ch 2 , — nh — o — ch 2 —, — ch 2 — n ( ch 3 )— o — ch 2 —[ known as a methylene ( methylimino ) or mmi backbone ], — ch 2 — o — n ( ch 3 )— ch 2 —, — ch 2 — n ( ch 3 )— n ( ch 3 )— ch 2 —, and — o — n ( ch 3 )— ch 2 — ch 2 —[ wherein the native phosphodiester backbone is represented as — o — p — o — ch 2 —] of the above referenced u . s . pat . no . 5 , 489 , 677 , and the amide backbones of the above referenced u . s . pat . no . 5 , 602 , 240 . also preferred are oligonucleotides having morpholino backbone structures of the above - referenced u . s . pat . no . 5 , 034 , 506 . modified oligonucleotides may also contain one or more substituted sugar moieties . preferred oligonucleotides comprise one of the following at the 2 ′ position : oh ; f ; o -, s -, or n - alkyl ; o -, s -, or n - alkenyl ; o -, s - or n - alkynyl ; or o - alkyl - o - alkyl , wherein the alkyl , alkenyl and alkynyl may be substituted or unsubstituted c 1 to c 10 alkyl or c 2 to c 11 alkenyl and alkynyl . particularly preferred are o [( ch 2 ), o ] m ch 3 , o ( ch 2 ) n och 3 , o ( ch 2 ) n nh 2 , o ( ch 2 ) n ch 3 , o ( ch 2 ) n onh 2 , and o ( ch 2 ) n on [( ch 2 ) n ch 3 )] 2 , where n and m are from 1 to about 10 . other preferred oligonucleotides comprise one of the following at the 2 ′ position : c 1 to c 10 lower alkyl , substituted lower alkyl , alkaryl , aralkyl , o - alkaryl or o - aralkyl , sh , sch 3 , ocn , cl , br , cn , cf 3 , ocf 3 , soch 3 , so 2 ch 3 , ono 2 , no 2 , n 3 , nh 2 , heterocycloalkyl , heterocycloalkaryl , aminoalkylamino , polyalkylamino , substituted silyl , an rna cleaving group , a reporter group , an intercalator , a group for improving the pharmacokinetic properties of an oligonucleotide , or a group for improving the pharmacodynamic properties of an oligonucleotide , and other substituents having similar properties . a preferred modification includes 2 ′- methoxyethoxy ( 2 ′- o —- ch 2 ch 2 och 3 , also known as 2 ′- o -( 2 - methoxyethyl ) or 2 ′- moe ) ( martin et al ., helv . chim . acta 78 : 486 [ 1995 ]) i . e ., an alkoxyalkoxy group . a further preferred modification includes 2 ′- dimethylaminooxyethoxy ( i . e ., a o ( ch 2 ) 2 on ( ch 3 ) 2 group ), also known as 2 ′- dmaoe , and 2 ′- dimethylaminoethoxyethoxy ( also known in the art as 2 ′- o - dimethylaminoethoxyethyl or 2 ′- dmaeoe ), i . e ., 2 ′- o — ch 2 — o — ch 2 — n ( ch 2 ) 2 . other preferred modifications include 2 ′- methoxy ( 2 ′- o — ch 3 ), 2 ′- aminopropoxy ( 2 ′- och 2 ch 2 ch 2 nh 2 ) and 2 ′- fluoro ( 2 ′- f ). similar modifications may also be made at other positions on the oligonucleotide , particularly the 3 ′ position of the sugar on the 3 ′ terminal nucleotide or in 2 ′- 5 ′ linked oligonucleotides and the 5 ′ position of 5 ′ terminal nucleotide . oligonucleotides may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar . oligonucleotides may also include nucleobase ( often referred to in the art simply as “ base ”) modifications or substitutions . as used herein , “ unmodified ” or “ natural ” nucleobases include the purine bases adenine ( a ) and guanine ( g ), and the pyrimidine bases thymine ( t ), cytosine ( c ) and uracil ( u ). modified nucleobases include other synthetic and natural nucleobases such as 5 - methylcytosine ( 5 - me - c ), 5 - hydroxymethyl cytosine , xanthine , hypoxanthine , 2 - aminoadenine , 6 - methyl and other alkyl derivatives of adenine and guanine , 2 - propyl and other alkyl derivatives of adenine and guanine , 2 - thiouracil , 2 - thiothymine and 2 - thiocytosine , 5 - halouracil and cytosine , 5 - propynyl uracil and cytosine , 6 - azo uracil , cytosine and thymine , 5 - uracil ( pseudouracil ), 4 - thiouracil , 8 - halo , 8 - amino , 8 - thiol , 8 - thioalkyl , 8 - hydroxyl and other 8 - substituted adenines and guanines , 5 - halo particularly 5 - bromo , 5 - trifluoromethyl and other 5 - substituted uracils and cytosines , 7 - methylguanine and 7 - methyladenine , 8 - azaguanine and 8 - azaadenine , 7 - deazaguanine and 7 - deazaadenine and 3 - deazaguanine and 3 - deazaadenine . further nucleobases include those disclosed in u . s . pat . no . 3 , 687 , 808 . certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention . these include 5 - substituted pyrimidines , 6 - azapyrimidines and n - 2 , n - 6 and o - 6 substituted purines , including 2 - aminopropyladenine , 5 - propynyluracil and 5 - propynylcytosine . 5 - methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0 . 6 - 1 . 2 . degree . c . and are presently preferred base substitutions , even more particularly when combined with 2 ′- o - methoxyethyl sugar modifications . another modification of the oligonucleotides of the present invention involves chemically linking to the oligonucleotide one or more moieties or conjugates that enhance the activity , cellular distribution or cellular uptake of the oligonucleotide . such moieties include but are not limited to lipid moieties such as a cholesterol moiety , cholic acid , a thioether , ( e . g ., hexyl - 5 - tritylthiol ), a thiocholesterol , an aliphatic chain , ( e . g ., dodecandiol or undecyl residues ), a phospholipid , ( e . g ., di - hexadecyl - rac - glycerol or triethylammonium 1 , 2 - di - o - hexadecyl - rac - glycero - 3 - h - phosphonate ), a polyamine or a polyethylene glycol chain or adamantane acetic acid , a palmityl moiety , or an octadecylamine or hexylamino - carbonyl - oxycholesterol moiety . one skilled in the relevant art knows well how to generate oligonucleotides containing the above - described modifications . the present invention is not limited to the antisense oligonucleotides described above . any suitable modification or substitution may be utilized . it is not necessary for all positions in a given compound to be uniformly modified , and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide . the present invention also includes antisense compounds that are chimeric compounds . “ chimeric ” antisense compounds or “ chimeras ,” in the context of the present invention , are antisense compounds , particularly oligonucleotides , which contain two or more chemically distinct regions , each made up of at least one monomer unit , i . e ., a nucleotide in the case of an oligonucleotide compound . these oligonucleotides typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation , increased cellular uptake , and / or increased binding affinity for the target nucleic acid . an additional region of the oligonucleotide may serve as a substrate for enzymes capable of cleaving rna : dna or rna : rna hybrids . by way of example , rnaseh is a cellular endonuclease that cleaves the rna strand of an rna : dna duplex . activation of rnase h , therefore , results in cleavage of the rna target , thereby greatly enhancing the efficiency of oligonucleotide inhibition of gene expression . consequently , comparable results can often be obtained with shorter oligonucleotides when chimeric oligonucleotides are used , compared to phosphorothioate deoxyoligonucleotides hybridizing to the same target region . cleavage of the rna target can be routinely detected by gel electrophoresis and , if necessary , associated nucleic acid hybridization techniques known in the art . chimeric antisense compounds of the present invention may be formed as composite structures of two or more oligonucleotides , modified oligonucleotides , oligonucleosides and / or oligonucleotide mimetics as described above . the present invention also includes pharmaceutical compositions and formulations that include the antisense compounds of the present invention as described below . the present invention contemplates the use of any genetic manipulation for use in modulating the expression of cancer markers of the present invention . examples of genetic manipulation include , but are not limited to , gene knockout ( e . g ., removing a herv - k ( hml - 2 ) gene from the chromosome using , for example , recombination ), expression of antisense constructs with or without inducible promoters , and the like . delivery of nucleic acid construct to cells in vitro or in vivo may be conducted using any suitable method . a suitable method is one that introduces the nucleic acid construct into the cell such that the desired event occurs ( e . g ., expression of an antisense construct ). genetic therapy may also be used to deliver sirna or other interfering molecules that are expressed in vivo ( e . g ., upon stimulation by an inducible promoter ( e . g ., an androgen - responsive promoter )). introduction of molecules carrying genetic information into cells is achieved by any of various methods including , but not limited to , directed injection of naked dna constructs , bombardment with gold particles loaded with said constructs , and macromolecule mediated gene transfer using , for example , liposomes , biopolymers , and the like . preferred methods use gene delivery vehicles derived from viruses , including , but not limited to , adenoviruses , retroviruses , vaccinia viruses , and adeno - associated viruses . because of the higher efficiency as compared to retroviruses , vectors derived from adenoviruses are the preferred gene delivery vehicles for transferring nucleic acid molecules into host cells in vivo . adenoviral vectors have been shown to provide very efficient in vivo gene transfer into a variety of solid tumors in animal models and into human solid tumor xenografts in immune - deficient mice . examples of adenoviral vectors and methods for gene transfer are described in pct publications wo 00 / 12738 and wo 00 / 09675 and u . s . pat . nos . 6 , 033 , 908 , 6 , 019 , 978 , 6 , 001 , 557 , 5 , 994 , 132 , 5 , 994 , 128 , 5 , 994 , 106 , 5 , 981 , 225 , 5 , 885 , 808 , 5 , 872 , 154 , 5 , 830 , 730 , and 5 , 824 , 544 , each of which is herein incorporated by reference in its entirety . vectors may be administered to subject in a variety of ways . for example , in some embodiments of the present invention , vectors are administered into tumors or tissue associated with tumors using direct injection . in other embodiments , administration is via the blood or lymphatic circulation ( see e . g ., pct publication 99 / 02685 herein incorporated by reference in its entirety ). exemplary dose levels of adenoviral vector are preferably 10 8 to 10 11 vector particles added to the perfusate . in some embodiments , the present invention provides antibodies that target tumors that express a cancer marker of the present invention ( e . g ., herv - k ( hml - 2 ) or associated target proteins ). any suitable antibody ( e . g ., monoclonal , polyclonal , or synthetic ) may be utilized in the therapeutic methods disclosed herein . in preferred embodiments , the antibodies used for cancer therapy are humanized antibodies . methods for humanizing antibodies are well known in the art ( see e . g ., u . s . pat . nos . 6 , 180 , 370 , 5 , 585 , 089 , 6 , 054 , 297 , and 5 , 565 , 332 ; each of which is herein incorporated by reference ). in some embodiments , the therapeutic antibodies comprise an antibody generated against a cancer marker of the present invention ( e . g ., herv - k ( hml - 2 )), wherein the antibody is conjugated to a cytotoxic agent . in such embodiments , a tumor specific therapeutic agent is generated that does not target normal cells , thus reducing many of the detrimental side effects of traditional chemotherapy . for certain applications , it is envisioned that the therapeutic agents will be pharmacologic agents that will serve as useful agents for attachment to antibodies , particularly cytotoxic or otherwise anticellular agents having the ability to kill or suppress the growth or cell division of endothelial cells . the present invention contemplates the use of any pharmacologic agent that can be conjugated to an antibody , and delivered in active form . exemplary anticellular agents include chemotherapeutic agents , radioisotopes , and cytotoxins . the therapeutic antibodies of the present invention may include a variety of cytotoxic moieties , including but not limited to , radioactive isotopes ( e . g ., iodine - 131 , iodine - 123 , technetium - 99m , indium - 111 , rhenium - 188 , rhenium - 186 , gallium - 67 , copper - 67 , yttrium - 90 , iodine - 125 or astatine - 211 ), hormones such as a steroid , antimetabolites such as cytosines ( e . g ., arabinoside , fluorouracil , methotrexate or aminopterin ; an anthracycline ; mitomycin c ), vinca alkaloids ( e . g ., demecolcine ; etoposide ; mithramycin ), and antitumor alkylating agent such as chlorambucil or melphalan . other embodiments may include agents such as a coagulant , a cytokine , growth factor , bacterial endotoxin or the lipid a moiety of bacterial endotoxin . for example , in some embodiments , therapeutic agents will include plant -, fungus - or bacteria - derived toxin , such as an a chain toxins , a ribosome inactivating protein , . alpha .- sarcin , aspergillin , restrictocin , a ribonuclease , diphtheria toxin or pseudomonas exotoxin , to mention just a few examples . in some preferred embodiments , deglycosylated ricin a chain is utilized . in any event , it is proposed that agents such as these may , if desired , be successfully conjugated to an antibody , in a manner that will allow their targeting , internalization , release or presentation to blood components at the site of the targeted tumor cells as required using known conjugation technology ( see , e . g ., ghose et al ., methods enzymol ., 93 : 280 [ 1983 ]). for example , in some embodiments the present invention provides immunotoxins targeted a cancer marker of the present invention ( e . g ., herv - k ( hml - 2 )). immunotoxins are conjugates of a specific targeting agent typically a tumor - directed antibody or fragment , with a cytotoxic agent , such as a toxin moiety . the targeting agent directs the toxin to , and thereby selectively kills , cells carrying the targeted antigen . in some embodiments , therapeutic antibodies employ crosslinkers that provide high in vivo stability ( thorpe et al ., cancer res ., 48 : 6396 [ 1988 ]). in other embodiments , particularly those involving treatment of solid tumors , antibodies are designed to have a cytotoxic or otherwise anticellular effect against the tumor vasculature , by suppressing the growth or cell division of the vascular endothelial cells . this attack is intended to lead to a tumor - localized vascular collapse , depriving the tumor cells , particularly those tumor cells distal of the vasculature , of oxygen and nutrients , ultimately leading to cell death and tumor necrosis . in preferred embodiments , antibody based therapeutics are formulated as pharmaceutical compositions as described below . in preferred embodiments , administration of an antibody composition of the present invention results in a measurable decrease in cancer ( e . g ., decrease or elimination of tumor ). the present invention further provides pharmaceutical compositions ( e . g ., comprising pharmaceutical agents that modulate the expression or activity of herv - k ( hml - 2 ) of the present invention ). the pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated . administration may be topical ( including ophthalmic and to mucous membranes including vaginal and rectal delivery ), pulmonary ( e . g ., by inhalation or insufflation of powders or aerosols , including by nebulizer ; intratracheal , intranasal , epidermal and transdermal ), oral or parenteral . parenteral administration includes intravenous , intraarterial , subcutaneous , intraperitoneal or intramuscular injection or infusion ; or intracranial , e . g ., intrathecal or intraventricular , administration . pharmaceutical compositions and formulations for topical administration may include transdermal patches , ointments , lotions , creams , gels , drops , suppositories , sprays , liquids and powders . conventional pharmaceutical carriers , aqueous , powder or oily bases , thickeners and the like may be necessary or desirable . compositions and formulations for oral administration include powders or granules , suspensions or solutions in water or non - aqueous media , capsules , sachets or tablets . thickeners , flavoring agents , diluents , emulsifiers , dispersing aids or binders may be desirable . compositions and formulations for parenteral , intrathecal or intraventricular administration may include sterile aqueous solutions that may also contain buffers , diluents and other suitable additives such as , but not limited to , penetration enhancers , carrier compounds and other pharmaceutically acceptable carriers or excipients . pharmaceutical compositions of the present invention include , but are not limited to , solutions , emulsions , and liposome - containing formulations . these compositions may be generated from a variety of components that include , but are not limited to , preformed liquids , self - emulsifying solids and self - emulsifying semisolids . the pharmaceutical formulations of the present invention , which may conveniently be presented in unit dosage form , may be prepared according to conventional techniques well known in the pharmaceutical industry . such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier ( s ) or excipient ( s ). in general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both , and then , if necessary , shaping the product . the compositions of the present invention may be formulated into any of many possible dosage forms such as , but not limited to , tablets , capsules , liquid syrups , soft gels , suppositories , and enemas . the compositions of the present invention may also be formulated as suspensions in aqueous , non - aqueous or mixed media . aqueous suspensions may further contain substances that increase the viscosity of the suspension including , for example , sodium carboxymethylcellulose , sorbitol and / or dextran . the suspension may also contain stabilizers . in one embodiment of the present invention the pharmaceutical compositions may be formulated and used as foams . pharmaceutical foams include formulations such as , but not limited to , emulsions , microemulsions , creams , jellies and liposomes . while basically similar in nature these formulations vary in the components and the consistency of the final product . agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical and other compositions of the present invention . for example , cationic lipids , such as lipofectin ( u . s . pat . no . 5 , 705 , 188 ), cationic glycerol derivatives , and polycationic molecules , such as polylysine ( wo 97 / 30731 ), also enhance the cellular uptake of oligonucleotides . the compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions . thus , for example , the compositions may contain additional , compatible , pharmaceutically - active materials such as , for example , antipruritics , astringents , local anesthetics or anti - inflammatory agents , or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention , such as dyes , flavoring agents , preservatives , antioxidants , opacifiers , thickening agents and stabilizers . however , such materials , when added , should not unduly interfere with the biological activities of the components of the compositions of the present invention . the formulations can be sterilized and , if desired , mixed with auxiliary agents , e . g ., lubricants , preservatives , stabilizers , wetting agents , emulsifiers , salts for influencing osmotic pressure , buffers , colorings , flavorings and / or aromatic substances and the like which do not deleteriously interact with the nucleic acid ( s ) of the formulation . certain embodiments of the invention provide pharmaceutical compositions containing ( a ) one or more antisense compounds and ( b ) one or more other chemotherapeutic agents that function by a non - antisense mechanism . examples of such chemotherapeutic agents include , but are not limited to , anticancer drugs such as daunorubicin , dactinomycin , doxorubicin , bleomycin , mitomycin , nitrogen mustard , chlorambucil , melphalan , cyclophosphamide , 6 - mercaptopurine , 6 - thioguanine , cytarabine ( ca ), 5 - fluorouracil ( 5 - fu ), floxuridine ( 5 - fudr ), methotrexate ( mtx ), colchicine , vincristine , vinblastine , etoposide , teniposide , cisplatin and diethylstilbestrol ( des ). anti - inflammatory drugs , including but not limited to nonsteroidal anti - inflammatory drugs and corticosteroids , and antiviral drugs , including but not limited to ribivirin , vidarabine , acyclovir and ganciclovir , may also be combined in compositions of the invention . other non - antisense chemotherapeutic agents are also within the scope of this invention . two or more combined compounds may be used together or sequentially . dosing is dependent on severity and responsiveness of the disease state to be treated , with the course of treatment lasting from several days to several months , or until a cure is effected or a diminution of the disease state is achieved . optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient . the administering physician can easily determine optimum dosages , dosing methodologies and repetition rates . optimum dosages may vary depending on the relative potency of individual oligonucleotides , and can generally be estimated based on ec 50 s found to be effective in in vitro and in vivo animal models or based on the examples described herein . in general , dosage is from 0 . 01 μg to 100 g per kg of body weight , and may be given once or more daily , weekly , monthly or yearly . the treating physician can estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues . following successful treatment , it may be desirable to have the subject undergo maintenance therapy to prevent the recurrence of the disease state , wherein the oligonucleotide is administered in maintenance doses , ranging from 0 . 01 μg to 100 g per kg of body weight , once or more daily , to once every 20 years . in some embodiments , the present invention provides compositions , kits , and methods for managing patient care . for example , in some embodiments , a diagnostic test that detects the presence of , or amount of , a herv - k ( hml - 2 ) marker is conducted before an appropriate therapy is applied ( i . e ., test , then treat ). in some embodiments , herv - k ( hml - 2 ) markers are detected after treatment to monitor the success of the treatment and allow the treating physician to alter the treatment ( e . g ., change the compound , change the dose , discontinue , etc .) if needed or desired ( i . e ., treat and test , which in some embodiments , involves testing , then treating , then testing ). in some embodiments , depending on the outcome of the diagnostic test , therapy is altered ( i . e ., treat , test , treat ). plasma samples were collected from newly diagnosed lymphoma patients . subjects with chronic lymphocytic leukemia were not included . samples were obtained from over 150 patients with new onset lymphoma . herv k ( hml2 ) was measured in each samples using quantitative rt pcr assay that measures gag viral rna ( see fig1 ). this assay indicates that in untreated lymphoma there is a considerable level of free herv k ( hml2 ) in plasma with non hiv associated dlcbl and hd having the highest levels of virus while patients with follicular lymphoma have somewhat lower levels of virus . the rt pcr does not distinguish type 1 from type 2 herv k ( hml2 ). a nucleic acid sequence based amplification assay ( nasba ) was developed which allows type 1 and type 2 env to be distinguished in plasma . the assay was applied to a subset of the fl patients and to patients with dlbcl . patients with fl with disease limited to isolated nodes and skin lesions had lower levels of viremia than those who , on bone marrow examination , were found to have lymphoma cells in the marrow as judged by flow based assays and or by immunocytogenetic analysis ( see fig2 ). levels of antibody to the rec protein were examined . rec is only be made by actively replicating virions . patients with dlcbl , and hd had rather high levels of antibody to this protein while those with fl had slightly lower levels in contrast to normal patients who donated plasma samples who rarely had antibody to . the high levels of endogenous virus in plasma is similar to the recent studies of an epidemic of lymphoma in the australian koala bear . east coast koalas have been dying of lymphoma . scientists studying these animals have discovered a new retrovirus virus called korv . this virus appears to have become endogenized in the koala in the past century from a virus similar to the gibbon ape leukemia virus ( galv ). koalas that have this endogenous virus in their genome at birth develop progressive korv viremia as they age and at the peak of viremia develop an aggressive often fatal lymphoma . the prolonged korv viremia that occurs in the koala prior to onset of lymphoma is similar to the prolonged herv k ( hml2 ) viremia that we have documented in some hiv lymphoma patients in whom we have been able to measure herv k ( hml2 ) viral load years before the onset of lymphoma . this indicates that herv k ( hml2 ) becomes more infectious as time progresses causing a gradual rise in viral load and that in both hiv lymphoma and non hiv lymphoma , some recombinant or some new virus which arises through complementation may form in these plasmas which now begins to have oncogenic potential and infectious potential . the hamster cho cell line can become infected with plasma associated virus from lymphoma patients . hiv associated lymphoma is dramatically reduced by highly active antiretroviral therapy ( haart ). this phenomenon suggests that improved immunity as a result of haart allows for better immune surveillance of cancer cells and or better control of ebv and hhv8 . this phenomenon further indicates that one or more retroviruses (( e . g ., herv - k ( hml - 2 ) has a causative effect on lymphoma . control of hiv tat may also be important in reducing oncogenic risk . experiments performed during development of embodiments of the present invention indicate that the antivirals that treat hiv , especially the nucleoside reverse transcriptase inhibitors , also have an effect on the replicative capacity of herv k ( hml2 ) and thereby indirectly reduce the activity of these viruses . data indicated that these viruses play a role in lymphoma oncogenesis , and that antivirals against herv k ( hml2 ) reduce the risk of development of lymphoma and improve survival from lymphoma . patients treated for lymphoma might show a reduction of the herv k ( hml2 ) viral load with successful lymphoma treatment . it has been demonstrated in a small group of hiv patients with different lymphomas that there was a marked drop of the herv k ( hml - 2 ) viral load commensurate with successful cancer chemotherapy ( see fig3 ). hiv antivirals were assayed to determine which antiviral agents have an antiviral effect against herv k ( hml2 ). the nccit cell line derived from a teratocarcinoma produces many herv k ( hml2 ) viral particles . nccit cells were maintained at 40 % confluence in 6 - well plates in rpmi medium and incubated for 7 days in the presence of increasing doses of nucleoside or non - nucleoside reverse transcriptase inhibitors or hiv protease inhibitors . drugs , provided as lyophilized powders by the aids research and reference reagent program , were resuspended to a final concentration of 10 mg / ml ( except for pfa : 60 mg / ml ) in different solvents as recommended ( see table 1 ). cells were incubated for 7 days at increasing doses of drugs or the vehicle of solution as controls . supernatants were collected and cell debris was removed by centrifugation at 2300 rpm for 20 min . supernatant was assessed for reverse transcriptase activity using the reverse transcription assay kit ( invitrogen ) as described by the manufacturer . in addition , supernatants were treated with 20 units of dnase ( roche ) for 1 hour at 37 ° c . and viral rna was extracted using the viral rna mini kit ( qiagen ) as described by the manufacturer . the herv - k type 2 viral load was measured by quantitative real time rt - pcr using primers that expand the type - 2 env gene region , which is absent in type - 1 viruses , kenv type2f : 5 ′- aga cac cgc aat cga gca ccg ttg a - 3 ′ ( seq id no . 1 ), and kenv type2r : 5 ′- atc aag gct gca agc agc ata ctc - 3 ′ ( seq id no . 2 ). standard curves were generated using serial dilutions of in vitro rna transcripts as external calibrators . in a similar way , quantities of herv - k type 2 proviruses were measured by real time pcr using 500 ng of isolated dna . the nrtis produced reduction in the herv k ( hml2 ) rt activity as shown for lamivudine and tenofovir disoproxil , azt , ftc , ddc , abacavir , β - d hydroxycytidine , d4t , and ddi ( see fig4 a - i ). the other agents notably azidothymidine , didianosine , emtricitabine abacavir and stavudine all had activity while there was no activity from the nnrt is medications and or the protease or entry inhibitors . these latter drugs which have been designed for specific viral targets would not be expected to have activity against herv k ( hml2 ). however , it is contemplated that other protease inhibitors , entry inhibitors , and non - nucleoside inhibitors may demonstrate activity . in addition , herv k - hml2 viral rna was also reduced ( see fig5 ). nrti antivirals can be given to patients with lymphoma to reduce the viral load of herv k ( hml2 ) in plasma and provide an antitumor effect on lymphoma which would demonstrate a causative role for herv k ( hml2 ) viruses in lymphoma . plasma samples were collected from patients who developed diffuse large b cell lymphoma as a complication of hiv infection before and after the diagnosis of lymphoma . rna extracted from the plasma samples using the qiaamp viral rna mini kit ( qiagen , inc . valencia , calif .) was subjected to rt - pcr using env - specific primers antecedent to sequencing the rt - pcr products . genotypic trees assembled by comparing env sequences from plasma samples to known herv k hml - 2 retrovirus sequences within the human genome revealed patient specific genotypes comprising hml2 type 1 or type 2 viral sequences , and / or recombinant sequences between type 1 and type 1 viruses , type 2 and type 2 viruses , and / or type 1 and type 2 viruses . accordingly , env sequences obtained from plasma samples find use to identify competent viruses indicative of herv k hml2 replication and the presence of lymphoma . in some embodiments , plasma samples are subjected to detection or analysis ( e . g ., sequencing ) using , for example , beads , microarrays , pores , and other solid and fluid high - 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