Compounds and methods useful for detection and treatment of cancer

Abstract

The present invention relates to compounds and methods useful for the detection and treatment of disorders associated with frameshift mutations in coding microsatellite regions. The compounds and methods are applicable in cancers, especially of DNA mismatch repair deficient (MMR) sporadic tumors and HNPCC associated tumors. The compounds are useful for detection of disorders and in therapy such as immuno-therapy. The diagnostic methods relate to diagnosis and prognostic assessment of disorders associated with frameshift polypeptides originating from frameshift mutations in coding microsatellite regions of genes based on the detection of immunological entities directed against said frameshift polypeptides in body fluids. With respect to the treatment of cancer, the invention pertains to methods which use immuno therapy with combinatorial mixtures of tumor specific frameshift peptides to elicit a cytotoxic T-cell response specifically directed against tumor cells for prevention and curative treatment of cancers and pre-cancers.

We claim: 
     
         1 . A method for selecting a subgroup in a colorectal cancer patient population having cancer cells associated with frameshift mutations in coding microsatellite regions, comprising:
 detecting the presence or absence of antibodies or antigen-recognizing cells directed against one or more frameshift polypeptides in biological samples from colorectal cancer patients, wherein the frameshift polypeptide is derived from a frameshift mutation in the A11 repeats in a coding microsatellite region of a gene selected from the group consisting of TAF1B, MACS, and HT001, and   selecting a subgroup of the colorectal cancer patients that have the antibodies or the antigen-recognizing cells present in their samples.   
     
     
         2 . The method of  claim 1 , wherein the frameshift polypeptide is derived from the A11 repeat of the TAF1B gene. 
     
     
         3 . The method of  claim 1 , wherein the frameshift polypeptide is derived from the A11 repeat of the HT001 gene. 
     
     
         4 . The method of  claim 1 , wherein the frameshift polypeptide is derived from the A11 repeat of the MACS gene. 
     
     
         5 . The method of  claim 1 , which measures the presence or absence of the antibodies. 
     
     
         6 . The method of  claim 1 , which measures the presence or absence of the antigen-recognizing cells.