Tyrosinase-related
protein (TRP) 2 belongs to the melanocyte
differentiation antigens and has been implicated as a target for
immunotherapy of human as well as murine
melanoma. In the current report, we explored the efficacy of nonmutated
epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated,
tumor-reactive immunity in vivo within the established
B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived
epitopes for vaccination provides a mouse model that closely mimics human
melanoma without introduction of xenogeneic or otherwise foreign
antigen. The results demonstrate that vaccination with
TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both
B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous
tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the
peptides used for vaccination. In contrast, within this autologous model, vaccination with
TRP2 peptide in
Freund's adjuvant or TRP2-encoding plasmid
DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based
vaccines to induce immunity against autologous
tumor-associated
antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.