Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer

Abstract

This invention relates to LY6G6F, VSIG10, TMEM25 and LSR proteins, which are suitable targets for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders, and drug development. This invention further relates to soluble LY6G6F, VSIG10, TMEM25 and LSR molecules, extracellular domains of LY6G6F, VSIG10, TMEM25 and LSR and conjugates, which are suitable drugs for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders. This invention further relates to antibodies and antigen binding fragments and conjugates containing same, and/or alternative scaffolds, specific for LY6G6F, VSIG10, TMEM25 or LSR molecules, which are suitable drugs for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders.

1 - 21 . (canceled) 
     
     
         22 . A monoclonal or polyclonal antibody or an antigen binding fragment thereof comprising an antigen binding site that binds specifically to an isolated polypeptide consisting essentially of an amino acid sequence as set forth in any one of SEQ ID NOs: 3-6, 60, 61, 82-93 or 97-100. 
     
     
         23 . The antibody or the antigen binding fragment of  claim 22 , wherein the antigen binding site comprises a conformational or linear epitope, and wherein the antigen binding site contains about 3-7 contiguous or non-contiguous amino acids. 
     
     
         24 . The antibody or fragment according to  claim 23 , wherein the antibody is a fully human antibody, chimeric antibody, humanized or primatized antibody. 
     
     
         25 . The antibody or the antigen binding fragment according to  claim 23 , wherein the antibody is selected from the group consisting of Fab, Fab′, F(ab′)2, F(ab′), F(ab), Fv or scFv fragment and minimal recognition unit. 
     
     
         26 . The antibody or the antigen binding fragment according to  claim 25 , wherein the antibody is coupled to a moiety selected from a drug, a radionuclide, a fluorophore, an enzyme, a toxin, a therapeutic agent, or a chemotherapeutic agent, and wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound. 
     
     
         27 . The antibody or the antigen binding fragment of  claim 22 , wherein said antibody blocks or inhibits the interaction of a VSIG10 polypeptide with a counterpart, wherein said VSIG10 polypeptide is a polypeptide consisting essentially of the amino acid sequence set forth in any one of SEQ ID NOs: 3, 4, 5, 6, 60, 61; 82-93, or 97-100. 
     
     
         28 . (canceled) 
     
     
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         30 . (canceled) 
     
     
         31 . A pharmaceutical composition comprising an antibody according to  claim 22 , and further comprising a pharmaceutically acceptable diluent or carrier. 
     
     
         32 . (canceled) 
     
     
         33 . A method for treating a subject in need thereof for cancer, the method comprising administering to the subject an antibody according to  claim 22 . 
     
     
         34 . (canceled) 
     
     
         35 . A method of performing one or more of the following in a subject:
 a. upregulating cytokines;   b. inducing expansion of T cells;   c. promoting antigenic specific T cell immunity;   d. promoting CD4+ and/or CD8+ T cell activation;   
       comprising administering an antibody according to  claim 22  to the subject. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 33 , wherein the treatment is combined with another moiety or therapy useful for treating cancer. 
     
     
         48 . The method of  claim 47 , wherein the therapy is radiation therapy, antibody therapy, chemotherapy, photodynamic therapy, adoptive T cell therapy, Treg depletion, surgery or in combination therapy with conventional drugs. 
     
     
         49 . The method of  claim 48 , wherein the moiety is selected from the group consisting of immunosuppressants, cytotoxic drugs, tumor vaccines, antibodies (e.g. bevacizumab, erbitux), peptides, pepti-bodies, small molecules, chemotherapeutic agents such as cytotoxic and cytostatic agents (e.g. paclitaxel, cisplatin, vinorelbine, docetaxel, gemcitabine, temozolomide, irinotecan, 5FU, carboplatin), immunological modifiers such as interferons and interleukins, immunostimulatory antibodies, growth hormones or other cytokines, folic acid, vitamins, minerals, aromatase inhibitors, RNAi, Histone Deacetylase Inhibitors, and proteasome inhibitors. 
     
     
         50 . The method of  claim 33  wherein the cancer is selected from a group consisting of breast cancer, cervical cancer, ovary cancer, endometrial cancer, melanoma, bladder cancer, lung cancer, pancreatic cancer, colon cancer, prostate cancer, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, Burkitt's lymphoma, multiple myeloma, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, myeloid leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia, thyroid cancer, thyroid follicular cancer, myelodysplastic syndrome (MDS), fibrosarcomas and rhabdomyosarcomas, melanoma, uveal melanoma, teratocarcinoma, neuroblastoma, glioma, glioblastoma, benign tumor of the skin, keratoacanthomas, renal cancer, anaplastic large-cell lymphoma, esophageal squamous cells carcinoma, hepatocellular carcinoma, follicular dendritic cell carcinoma, intestinal cancer, muscle-invasive cancer, seminal vesicle tumor, epidermal carcinoma, spleen cancer, bladder cancer, head and neck cancer, stomach cancer, liver cancer, bone cancer, brain cancer, cancer of the retina, biliary cancer, small bowel cancer, salivary gland cancer, cancer of uterus, cancer of testicles, cancer of connective tissue, prostatic hypertrophy, myelodysplasia, Waldenstrom's macroglobinaemia, nasopharyngeal, neuroendocrine cancer, myelodysplastic syndrome, mesothelioma, angiosarcoma, Kaposi's sarcoma, carcinoid, oesophagogastric, fallopian tube cancer, peritoneal cancer, papillary serous mullerian cancer, malignant ascites, gastrointestinal stromal tumor (GIST), Li-Fraumeni syndrome and Von Hippel-Lindau syndrome (VHL), and wherein the cancer is non-metastatic, invasive or metastatic. 
     
     
         51 . The method of  claim 50 , wherein the cancer is any of melanoma, cancer of liver, renal, brain, breast, colon, lung, ovary, pancreas, prostate, stomach, multiple myeloma, Hodgkin's lymphoma, non Hodgkin's lymphoma, acute and chronic lymphoblastic leukemia and acute and chronic myeloid leukemia. 
     
     
         52 . A method for potentiating a secondary immune response to an antigen in a subject, which method comprises administering the antigen to the subject, wherein the antigen is a cancer antigen; and administering effective amount of an antibody according to  claim 22  to the subject. 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . A method of using an antibody according to  claim 22  as a cancer vaccine adjuvant, comprising administration to a patient an immunogenic amount of a tumor associated antigen preparation of interest; and a cancer vaccine adjuvant in a formulation suitable for immunization, wherein the immune response against the tumor associated antigen in the presence of the cancer vaccine adjuvant is stronger than in the absence of the cancer vaccine adjuvant. 
     
     
         56 - 69 . (canceled) 
     
     
         70 . The method of  claim 35 , further comprising treating cancer through administration of said antibody to the subject.