Genetic immunization of mice with human tyrosinase-related protein 2: Implications for the immunotherapy of melanoma

The melanosomal protein TRP2 expressed by melanocytes and most melanoma cel ls is an attractive, clinically relevant model antigen for the experimental development of melanoma immunotherapy in mice. A peptide shared by murine and human TRP2 can be recognized by melanoma-reactive CTL in C57BL/6 mice, as well as in human melanoma patients. Previous experiments demonstrated th at gene gun immunization of mice with plasmid DNA encoding autologous murin e TRP2 was unable to induce protective immunity against B16 melanoma cells naturally expressing TRP2. In the present study, we investigated whether th e use of cDNA encoding xenogeneic human TRP2, which is highly homologous to murine TRP2, would be more effective. Genetic immunization of mice with hu man TRP2. resulted in coat depigmentation as a sign of autoimmune-mediated destruction of melanocytes and provided significant protection against meta static growth of B16 melanoma. Induction of protective immunity was associa ted with TRP2-reactive antibodies and CD8(+) T cells. Furthermore, immuniza tion with recombinant adenovirus was more effective than immunization with plasmid DNA using the gene gun. Our results provide new insights for the de velopment of antigen-specific immunotherapy of melanoma, Int. J. Cancer 86: 89-94, 2000. (C) 2000 Wiley-Liss, Inc.