It has recently become evident that effective activation of T cells requires, in addition to TCR-mediated signals, costimulatory signals. These studies have led to the hypothesis that lack of adequate costimulation of T cells may, at least in part, be responsible for tumors to escape host immunity. Current efforts are focused on both understanding the interactions of these molecules and identifying novel costimulatory molecules. It is unclear whether tumor antigen-specific T cells are tolerated in cancer patients and in experimental tumor models.
Recent studies indicate that immunological ignorance rather than tolerance is prevalent.
We are generating the transgenic mice bearing specific T cell receptors to a murine tumor antigen to facilitate functional analysis of tumor antigen-specific T cells in vivo. We are also identifying the role of costimulatory molecules in breaking tolerance or reversing ignorance in these tumor models. Both in vivo or in vitro analyses of T cells will shed light on molecular mechanisms that lead to the tumor progression. Development of potent cancer vaccines aimed at activating T cell-mediated immune response requires the knowledge of tumor antigens. Work in our laboratory has been focused on characterizing MHC-associated peptide by HPLC and mass spectrometer and on screening cDNA library of tumor lines by CTL assay.