Abstract 4576: Immunization with CPG in combination with MHC class I and class II peptides stimulates rapid and strong tumor antigen-specific CTL responses in melanoma patients.

Abstract

Abstract There is now ample evidence that the toll-like receptor 9 ligand CPG/PF-3512676 represents a potent adjuvant for peptide/protein-based cancer vaccines capable of stimulating ex vivo detectable tumor antigen (TA)-specific CD8+ T cell responses in patients with advanced melanoma. Although CD4+ T cells appeared to promote the expansion and functions of CD8+ T cells in experimental models, melanoma-associated helper peptides have been shown to paradoxically decrease CD8+ T cell responses to a multipeptide melanoma vaccine emulsified in Montanide, possibly by inducing antigen-specific Tregs. To further investigate this question, we have performed one Phase I study of immunization where patients with advanced melanoma were immunized with CPG, Montanide and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V either alone (Arm 1, n=5) or in combination with the pan-DR CD4 helper peptide NY-ESO-1 119-143 (Arm 2, n=7). Patients in both arms exhibited a rapid increase of NY-ESO-1-specific CD8+ T cells that were detectable ex vivo by flow cytometry. Strikingly, the mean frequency of vaccine-induced NY-ESO-1-specific CD8+ T cells after 6 biweekly immunizations was five times higher in patients who also received the helper peptide. Melanoma patients immunized with the helper peptide (Arm 2) developed a rapid increase of Foxp3− NY-ESO-1-specific CD4+ T cells that produced Th-1 type cytokines and IL-21 ex vivo. As compared to Arm 1, melanoma patients included in Arm 2 developed vaccine-induced NY-ESO-1-specific CD8+ T cells that were more differentiated, produced more IFN-γ and exhibited higher cytolytic functions in ex vivo assays. Collectively, our data support the inclusion of well-defined MHC class II peptides in combination with CPG/PF-3512676 and MHC class I peptides in multipeptide melanoma vaccines to better augment the expansion, differentiation, IFN-γ production and lytic function of TA-specific CTLs in patients with advanced melanoma. This work was supported by the National Institutes of Health/National Cancer Institute grants R01CA90360 and R01CA157467 (to H.M. Zarour). Citation Format: Julien Fourcade, Zhaojun Sun, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, Stergios Moschos, Ahmad Tarhini, Hussein Tawbi, John M. Kirkwood, Hassane M. Zarour. Immunization with CPG in combination with MHC class I and class II peptides stimulates rapid and strong tumor antigen-specific CTL responses in melanoma patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4576. doi:10.1158/1538-7445.AM2013-4576