The investigator's goal is to determine whether a novel assay for peptide-specific CD8+ T cell responses to cancer vaccines can be used to evaluate the immunological activity of the vaccines and to predict their clinical effectiveness. This proposal exploits several recent advances in the investigator's laboratory and clinic: 1) the development of a new assay for peptide-specific CD8+ T cells which is sufficiently sensitive to detect vaccine-induced increases in these cells in peripheral blood without the need for in vitro sensitization; 2) the identification of panels of peptides on important melanoma antigens which are recognized by human CD8+ T cells and have different HLA restrictions; and 3) the availability of a polyvalent melanoma antigen vaccine that contains these peptides. The specific goals of this project are to investigate: 1) Whether the induction of CD8+ T cells responses to defined antigens in a vaccine for melanoma can be used as a marker of the vaccine's immunological activity. 2) Whether the induction of CD8+ T cells to antigens in the vaccine is an intermediate marker of vaccine activity which is predictive of an improved clinical outcome, and the predictive value of this assay compared to other assays of vaccine immunogenicity. The study will be conducted in the context of ongoing clinical trials of a polyvalent vaccine for melanoma that contains multiple antigens recognized by CD8+ T cells. The potential clinical applications of this work include providing a method to evaluate the potency of cancer vaccines, an intermediate marker of vaccine activity which may be predictive of an improved clinical outcome, and identifying subsets of patients who are benefiting from vaccine treatment.
