Tumor Specific CD4+ T-Cell Costimulation Through a Novel Receptor/Ligand Interaction
Annual rept. 1 Aug 1998-31 Jul 1999
CHILES RESEARCH INST PORTLAND OR
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CD4 T cells specific for tumor antigens have been less well characterized than CD8 T cells. There appears to be two main reasons for this discrepancy 1 CD8 T cells isolated from tumor tumor infiltrating lymphocytes TIL preferentially expand in the presence of anti-CD3 and IL-2, and 2 CD4 T cells isolated from a tumor environment appear to be defective in signaling and therefore may not have the capacity to proliferate to tumortumor-associated Ag. We will attempt to bypass these limitations by using a novel approach to costimulate a tumor specific CD4 T cell memory response. Recently, we found that CD4 T cells isolated near the tumor sites of patients with melanoma and head and neck cancer expressed the OX-40 receptor, but not cells in the periphery of these same patients. It is our hypothesis that these OX-40 T cells were recently activated in vivo in response to tumor antigens. If a costimulatory signal could be provided to these OX-40 T cells by the OX-40 ligand, then clonal expansion of CD4 T cells specific tumor should occur. In this proposal, we will characterize OX-40 expression by human and mouse CD4 T cells specific for breast cancer and attempt to expand them both in vivo and in vitro with MHCII tumors transfected with the OX-40 ligand, in essence making the tumor an antigen presenting cell capable of priming CD4 T cell immunity.
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