Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2.

A potential approach to activate tumor-specific T cells is to use live bacterial vectors to deliver appropriate antigens in a highly immunostimulatory context. We constructed a recombinant strain of Listeria monocytogenes (rLM) expressing murine tyrosinase-related protein-2 (TRP-2), a nonmutated melanocyte-derived differentiation antigen highly expressed in melanomas. Immunization of C57Bl/6 mice with this rLM strain efficiently primed CD8 T cells to recognize the MHC class I-restricted TRP-2180-188 epitope and express IFN-gamma upon in vitro peptide stimulation. Peptide-loaded target cells were lysed in vitro by TRP-2-specific T cells in cytotoxicity assays, and mice immunized and boosted with rLM expressing TRP-2 were functionally protected from subcutaneous challenge with B16 melanoma cells. These results identify and characterize the anti-"self" T-cell responses induced by recombinant L. monocytogenes expressing an endogenous, nonmutated tumor antigen.