) Attempts have been made over the last several years to develop vaccines that would aid in the eradication of human malignancy. In general, these vaccines have not been effective. Recent advances in both basic immunology and molecular biology have demanded a re-evaluation of cancer vaccines. We now know that human tumors are immunogenic and have defined specific tumor antigens. Furthermore, we have a more detailed understanding of how T-cells recognize antigens, as peptide fragments presented in human MHC molecules. Finally, we have a better understanding of how tumors evade immune recognition, including the generation of antigen negative variants by an immune response that actually eradicated antigen bearing tumor cells. The development of antigen negative variants underscores the need for vaccines targeting multiple important antigens at a minimal disease state. This proposal will allow the identification and assessment of multiple potential antigens as candidates for a polyvalent vaccine with the 5-year goal of initiating a Phase I studies of a multiple antigen vaccines to evaluate the ability to generate immunity to multiple cancer causing proteins. The focus of my group is to develop cancer vaccines targeting breast, ovarian, prostate, and colon cancer for the prevention of cancer relapse.
The specific aims of this proposal are: (1) to determine whether pre-existing antigen specific cellular and humoral immune responses occur in patients with cancer bearing the candidate antigen as compared to a normal control population, (2) to determine the most effective vaccination strategy for augmenting existent immunity to a candidate antigen, in vivo, to potentially therapeutic levels, (3) to identify novel immunogenic proteins present in solid tumors that may serve as candidate antigens in the development of cancer vaccines, and (4) to determine in a series of limited Phase I clinical trials, whether a vaccine constructed of peptide epitopes or the DNA of a candidate antigen can elicit antigen specific immunity in patients with cancer bearing that antigen.
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