Vaccination of ovarian cancer patients with overlapping long peptides (OLP) from cancer-testis antigen NY-ESO-1 and poly-ICLC in Montanide-ISA-51 (Montanide) was found to consistently induce integrated immune responses (antibody, CD4+ and CD8+ T cells). Using detailed methods, we investigated the respective effects of poly-ICLC and Montanide adjuvant on pre- and post-vaccine NY-ESO-1-specific CD4+ T cells, because of their central function for induction and maintenance of both antibody and CD8+ T cells. Polyclonal NY-ESO-1-specific CD4+ T cell lines were generated from 12 patients using CD154-based selection of precursors before and after vaccination with either (I) OLP alone, (II) OLP in Montanide, or (III) OL... More
Vaccination of ovarian cancer patients with overlapping long peptides (OLP) from cancer-testis antigen NY-ESO-1 and poly-ICLC in Montanide-ISA-51 (Montanide) was found to consistently induce integrated immune responses (antibody, CD4+ and CD8+ T cells). Using detailed methods, we investigated the respective effects of poly-ICLC and Montanide adjuvant on pre- and post-vaccine NY-ESO-1-specific CD4+ T cells, because of their central function for induction and maintenance of both antibody and CD8+ T cells. Polyclonal NY-ESO-1-specific CD4+ T cell lines were generated from 12 patients using CD154-based selection of precursors before and after vaccination with either (I) OLP alone, (II) OLP in Montanide, or (III) OLP and poly-ICLC in Montanide. Kinetics, quantification, fine specificity, avidity, and cytokine-producing pattern were analyzed in-depth and compared between vaccine cohorts. Vaccination with OLP alone was not only unable to elicit CD4+ T cell responses but also suppressed high-avidity CD4+ T cell precursors that recognized naturally-processed NY-ESO-1 protein before vaccination. Emulsification of OLP in Montanide was required for the expansion of high-avidity NY-ESO-1-specific CD4+ T cell precursors. Poly-ICLC significantly enhanced CD4+ Th1 responses while suppressing the induction of IL-4-producing Th2 and IL-9-producing Th9 cells. In summary, Montanide and poly-ICLC had distinct and cooperative effects for the induction of NY-ESO-1-specific Th1 cells and integrated immune responses by OLP vaccination. These results support the use of admixing poly-ICLC in Montanide adjuvant to rapidly induce anti-tumor type-1 immune responses by OLP from self/tumor antigens in human cancer vaccines.
