The impact of a multi-epitope melanoma helper peptide vaccine on Th1 cytokine production by responding lymphocytes.

Abstract

e19028 Background: Melanomas produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. To describe the vaccine-induced production of Th2 or Th1 responses to helper peptides in the setting of advanced melanoma, we measured cytokine production of helper T cells responding to vaccination by 6 melanoma helper peptides (6MHP). We then analyzed results by measurable disease status. Methods: Thirty-nine patients with stage IIIB-IV melanoma received a 6MHP vaccine as a part of the UVA Mel41 clinical trial. For analysis of this correlative endpoint, antigen-reactive T cells were exposed to antigen, and supernatants (days 2 and 5) were assayed by cytokine bead arrays for Th1 and Th2 cytokines. Results: The dominant Th1 and Th2 cytokines detected were IFN-g and IL-5, respectively, though high levels of IL-2 were also produced early by sentinel lymph node lymphocytes. Th1 cytokine responses predominated both pre and post vaccine. Peripheral blood lymphocytes from patients with clinically measurable disease produced similar levels of total cytokine as patients with no evidence of disease (111pg/ml versus 174pg/ml respectively, p=0.44). For both disease statuses, the cytokine profile was Th1-dominant in most patients. Total cytokine production varied significantly among patients and varied over time but persisted up to nine months post-vaccine. Conclusions: The MHC class II-associated peptides used in this study induced helper T cells with a Th1-biased cytokine response in both PBMC and sentinel immunized nodes. However, both groups of patients can mount a Th1 dominant response to these peptides, which may persist long after the vaccination sequence. Future studies are needed to test newer vaccine adjuvants in combination with these peptides.