The overall long-term objective of this research program is to develop and investigate novel vaccine approaches for the immunotherapy of malignancy. It is apparent that experimental and human tumors express capable of being recognized by the immune system; however, the innate immunoresponse to progressive tumors is sufficient 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 dendritic cells are highly effective in processing and presenting antigens from a diverse array of tumors to naive T cells which are then capable of inducing tumor rejection responses. The major theme of this program project is the investigation of dendritic cell-based vaccines in the therapy of cancer. This program is comprised of three highly interactive projects and a core support structure as follows: Project by Mule: SLC and Dendritic Cells in Antitumor Immunity and Therapy Project by Chang: Immune Responses Induced by Tumor-Pulsed DC Project by Nickoloff: Dendritic Cell-Based Vaccines in Stage IV Melanoma Patients These projects are oriented toward clinical applications with each one involving experiments therapeutics studies in patients with refractory cancers. The populations which will be evaluated 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 dendritic cell- based vaccines. 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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