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Immune Responses to a Class II Helper Peptide Epitope in Patients with Stage III/IV Resected Melanoma

¹ Department of Medicine, Keck/University of Southern California School of Medicine, Los Angeles, California; ² Beckman Coulter Inc., San Diego, California; and ³ GlaxoSmithKline Biologicals, Rixensart, Belgium

The importance of CD8⁺ cytolytic T cells for protection from viral infection and in the generation of immune responses against tumors has been well established. In contrast, the role of CD4⁺ T-helper cells in human infection and in cancer immunity has yet to be clearly defined. In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4⁺ T-cell immune responses. Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4⁺ T cells from patients over the course of the 12-month vaccine regimen. The postvaccine CD4⁺ T cells exhibited a mixed T-helper 1/T-helper 2 phenotype, proliferated in response to the antigen and promiscuously recognized the peptide epitope bound to different human leukocyte antigen-DRß alleles. For 1 DRß1*0401⁺ patient, antigen-specific CD4⁺ T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted. These data establish the immunogenicity of a class II epitope derived from a melanoma-associated antigen and support the inclusion of class II peptides in future melanoma vaccine therapies.

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