The overall long-term objective of this research program is to develop and investigate novel gene transfer approaches for the immunotherapy of malignancy. It is apparent that experimental and human tumors express antigens capable of being recognized by the immune system; however, the innate immune response to progressive tumors is insufficient due to the weakness of the antigen and/or occurrence of tumor-induced immunosuppression. Over the last several years a large body of evidence has accumulated indicating that the immunogenicity of tumors can be significantly altered by genetic modification and represents the theme of this program. This program is comprised of three highly interactive projects and a core support structure as follows: Project 1: New Strategies to Improve Molecularly Engineered Tumor Vaccines. Project 2: Immune Responses Induced by Gene Transfer in humans Project 3: Immunotherapy by In Vivo Gene Transfer into Tumors Core: Immunology These projects are oriented towards clinical applications with each one involving experimental therapeutic studies in patients with refractory cancers. The populations which will be evaluated in each project include individuals with melanoma or colorectal cancer. Melanoma represents a tumor which has traditionally been examined in immunotherapeutic trials and appears to represent a weakly immunogenic neoplasm with identified tumor associated antigens. Colorectal cancer is postulated to be a poorly immunogenic tumor and has not been a cancer which has been adequately evaluated for immunotherapy. Inherent in all three projects will be the characterization of the cellular responses associated with the gene transfer strategies. It is anticipated that the information generated from the projects will provide important information about the antigens expressed on these cancers and their immunobiology.
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