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.
- Received July 5, 2013.
- Revision received August 28, 2013.
- Accepted September 7, 2013.
- Copyright © 2013, American Association for Cancer Research.