Development of new diagnostic and immunotherapeutic methods for patients with cancer

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We have established basics for development of new diagnostic and therapeutic methods for various cancers of digestive organs. 1) Identification of human tumor antigens and individualized immunotherapy : Various tumor antigens and T cell epitopes were identified by using systematic gene analysis and cDNA cloning using human IgG from immunodeficient mice implanted with human cancer tissues. The analysis of the immune responses revealed importance of individualized immunotherapy. Intratumoral administration of peptide pulsed dendritic cells was developed, and it resulted in induction of strong immune responses and anti-tumor effects through antigen spreading. 2) Immune responses to MSI^+ cancers : The immune response to tumor specific frameshift peptides was found to explain good prognosis of patients with MSI^+ cancers, indicating possible immunotherapy to MSI^+ cancers. The immune response to a cancer-testis antigen CAGE was frequently detected in the patients with MSI^+ cancers, sugges … More ting its use in the immunotherapy. 3) Mechanisms for immune escape of cancer cells : Using newly developed mutation specific viral shRNAs, enhanced MAPK signaling through the BRAF or RAS mutation was found to cause production of multiple immunosuppressive factors, indicating immunotherapy in combination with signal inhibitors. 4) Immunological implications of cancer stem cells and epithelial mescenchymal transition (EMT) : Differential expression of tumor antigens in the established stem like pancreatic cancer SP cells and EMT cells was found. EMT was found to enhance tumor metastasis through immunosuppression. 5) Clinical applications of the identified tumor antigens : IgG Abs for tumor antigens were found to be useful for prognostic diagnosis. Anti-p53 Ab was found to be useful for early diagnosis of colon cancer in the patients with ulcerative colitis. Tumor markers useful for diagnosis of high metastatic ability were identified. The identified tumor antigens and immune-interventions are expected to be evaluated in the future clinical trials. KU-CR4 is a potential target for antibody therapy. Less