Spontaneous immune responses to melanoma-associated antigens in melanoma, vitiligo and healthy controls

Abstract

9682 Background: To evaluate the immunogenicity of peptide-based vaccines for melanoma, it is of critical importance to provide immunological correlates by which to gauge clinically protective immune responses. A valuable model is the autoimmune disorder vitiligo in which there is evidence of the involvement of cellular immunity eliminating melanocytes through recognition of autoantigens. In mice, skin depigmentation develops after immunization with human tyrosinase-related protein (TRP)-2, suggesting a cytotoxic immune response against antigen-bearing cells, a desired result of vaccine therapies in melanoma. In addition, skin-homing melanocyte-specific cytotoxic T cells have been demonstrated in vitiligo patients. In this study we examined the underlying cellular immunity and the extent of these immune responses to several HLA A2-restricted melanoma-associated antigens (MAA) in patients with vitiligo and melanoma. Methods: We accrued 12 healthy volunteers (controls), 11 patients with malignant melanoma and 14 subjects with vitiligo, the study was IRB approved at Rockefeller University. Enzyme-linked immunospot assays (ELISPOT) were performed on peripheral blood mononuclear cells of HLA A2.1 positive patients to enumerate antigen-specific T-cells secreting interferon-gamma after exposure to the MAA. Five HLA A2-restricted melanoma-associated peptides: gp 100209–217, tyrosinase368–376, Melan A26–35, MAGE 3271–279, TRP-2180–188 were chosen as well as Flu-MP (positive control). Less than 50% of individuals were HLA A2.1 positive. Conclusions: In contrast to expected results, melanoma antigen-specific T cell responses were not observed in the peripheral blood of vitiligo subjects. Therefore, studies are planned utilizing more sensitive assays, different antigens and removal of regulatory T-cells. No significant financial relationships to disclose.