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.
Bruhn
Kevin W
KW
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1747, USA.
Craft
Noah
N
Nguyen
Bidong D
BD
Yip
Jimmy
J
Miller
Jeff F
JF
D000818:Animals; D000951:Antigens, Neoplasm / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000235:genetics; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000951:Antigens, Neoplasm; D011993:Recombinant Fusion Proteins; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase