Tumor-associated carbohydrate antigens (TACAs) are saccharides and oligosaccharides which show highly restricted expression on cancer cells. Since TACAs are unique to cancer cells, there is a great interest in generating an active immune response against TACAs as a means of reducing cancer metastasis or recurrence. TACAs are also useful biomarkers for evaluating the aggressiveness of the cancer. Two major challenges to using TACAs in active immunotherapy are their poor antigenicity and the inherent difficulty of synthesizing oligosaccharides and related glycoconjugates by chemical means. This application proposes to synthesize and study the antigenicity of TACA glycoconjugates. A key aspect of the proposal is the study of increased vaccine antigenicity mediated by xenobiotic carbohydrates unrelated to the TACAs. The xenobiotic carbohydrates are proposed to enhance antigenicity through anti- carbohydrate antibody-mediated mechanisms. This proposal takes advantage of a collaborative interaction between PIs trained in organic chemistry and immunology so that the antigenicity of all vaccines will be well characterized in mice.
This project will develop and evaluate the cellular and humor immune response of vaccines in mice that will serve as leads for human anti-cancer vaccines. Chemical approaches will be developed that will aid in generating diagnostic and therapeutic agents for the treatment of cancer.
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