Identification and use of novopeptides for the treatment of cancer

Abstract

Disclosed are compositions relating to novopeptides identified by the presence of frameshift mutations in tumor genes previously not identified as being oncogenic. The disclosed peptides can be used in the disclosed methods for the treatment of cancer.

1 . A method of identifying a novopeptide that produces an anti-cancer immune response, comprising:
 a. identifying a novopeptide by informatics, genomics, proteomics, or immunological screens; and   b. determining that the novopeptide induces an immune response that differentiates between tumor cells and normal cells.   
     
     
         2 . The method of  claim 1 , wherein the novopeptide of step a) is identified using cancer genome and expression databases to detect novopeptides preferentially expressed in tumor cells versus normal cells; using nucleic acid sequencing methods to detect alterations in DNA and or RNA that lead to the novopeptide; or using mass spectrometry to detect novopeptides that are on the tumor cell surface. 
     
     
         3 .- 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the novopeptide of step b) is identified using immune assays of human cancer patient serum or animal tumor model serum to detect reactivity to the novopeptide; or using immune assays of human cancer patient peripheral blood mononuclear cells (PBMCs) or animal tumor model (PBMCs) to detect reactivity to the novopeptide. 
     
     
         6 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the anti-cancer immune response of the novopeptide is further determined by administering a non-human animal homolog of a human novopeptide to the non-human animal in a prophylactic or therapeutic cancer model; and measuring the anti-cancer effect of the novopeptide in the animal model of cancer. 
     
     
         13 .- 18 . (canceled) 
     
     
         19 . A method of identifying a novopeptide that induces a protective immune response to cancer, comprising
 a. identifying a novopeptide by informatics (odds ratios of tumor to normals);   b. sequencing candidate DNA or RNA;   c. performing mass spectrometry on peptides eluted from MHCI of tumor cells and normal cells, and detecting the peptides that are expressed by tumor cells;   d. determining whether T-cells reactive to the novopeptide peptide react with MHCI matched tumor cells but not normal cells; or   e. determining if antibodies raised to the novopeptide react with tumor cells expressing the novopeptide and not with normal cells; or   f. determining both d. and e.   
     
     
         20 .- 27 . (canceled) 
     
     
         28 . A vaccine for a cancer comprising a novopeptide, wherein the novopeptide is tumor-specific antigen, and wherein the antigen is derived from a frameshift mutation of a non-oncogenic gene. 
     
     
         29 . The vaccine of  claim 28 , wherein the novopeptide comprises the sequence set forth in SEQ ID NO:2 SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8, or wherein the novopeptide comprises a frameshift of the SMC1 gene. 
     
     
         30 .- 33 . (canceled) 
     
     
         34 . The vaccine of  claim 28 , wherein the cancer is selected from the group of cancers consisting of lymphomas (Hodgkins and non-Hodgkins), B cell lymphoma, T cell lymphoma, leukemias, myeloid leukemia, carcinomas, carcinomas of solid tissues, squamous cell carcinomas, squamous cell carcinomas of the mouth, throat, larynx, and lung, adenocarcinomas, sarcomas, gliomas, high grade gliomas, blastomas, neuroblastomas, plasmacytomas, histiocytomas, melanomas, adenomas, hypoxic tumours, myelomas, AIDS-related lymphomas or sarcomas, metastatic cancers, mycosis fungoides, bladder cancer, brain cancer, nervous system cancer, lung cancers such as small cell lung cancer and non-small cell lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, hepatic cancer, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial cancer, renal cancer, genitourinary cancer, esophageal carcinoma, head and neck carcinoma, large bowel cancer, hematopoietic cancers, and testicular cancer. 
     
     
         35 . A method of preventing or treating a cancer comprising administering to a subject the vaccine of  claim 28   claim 34 . 
     
     
         36 .- 42 . (canceled) 
     
     
         43 . An antibody to tumor-specific antigen, wherein the antigen is a novopeptide identified by the steps comprising
 a. identifying a novopeptide by informatics, genomics, proteomics, or immunological screens; and   b. determining that the novopeptide induces an immune response that differentiates between tumor cells and normal cells.   
     
     
         44 . (canceled) 
     
     
         45 . The antibody of  claim 43 , wherein the novopeptide comprises the sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8, or wherein the novopeptide comprises a frameshift of the SMC1 gene. 
     
     
         46 .- 66 . (canceled) 
     
     
         67 . The antibody to the novopeptide or the novopeptide of  claim 43  for use in a method of diagnosing an individual with cancer comprising obtaining a tissue sample, and screening for the presence of a novopeptide or an immune response to a novopeptide, wherein the novopeptide comprises a frameshift mutation. 
     
     
         68 .- 72 . (canceled) 
     
     
         73 . The antibody to the novopeptide or the novopeptide of  claim 67 , wherein the frameshift mutation comprises the sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8, or wherein the frameshift mutation is a frameshift of the SMC1 Rene. 
     
     
         74 .- 77 . (canceled)