Immunization with analogue peptide in combination with CpG and Montanide expands tumor antigen-specific CD8+ T cells in melanoma patients

摘要

Analogue peptides represent a promising tool to further optimize peptide-based vaccines in promoting the expansion of tumor antigen-specific CTLs. Here, we report the results of a pilot trial designed to study the immunogenicity of the analogue peptide NY-ESO-1 157-165V in combination with CpG 7909/PF3512676 and Montanide ISA 720 in patients with stage III/IV NY-ESO-1-expressing melanoma. Eight Patients were immunized either with Montanide and CpG (arm 1, three patients), Montanide and peptide NY-ESO-1 157-165V (arm 2, two patients) or with Montanide, CpG and peptide NY-ESO-1 157-165V (arm 3, three patients). Only the three patients immunized with Montanide, CpG and peptide NY-ESO-1 157-165V in arm 3, developed a rapid increase of effector-memory NY-ESO-1-specific CD8+ T cells, detectable ex vivo. The majority of these cells exhibited an intermediate/late-stage differentiated phenotype (CD28⁻). Our study further demonstrated that our vaccine approach stimulated spontaneous tumor-reactive NY-ESO-1-specific CD8+ T cells in two patients with advanced disease but failed to prime tumor-reactive NY-ESO-1-specific T cells in one patient with no spontaneously tumor-induced CD8+ T cell responses to NY-ESO-1. Collectively, our data support the capability of the analogue peptide NY-ESO-1 157-165V in combination with CpG and Montanide to promote the expansion of NY-ESO-1-specific CD8+ T cells in patients with advanced cancer. They also suggest that the presence of tumor-induced NY-ESO-1-specific T cells of well-defined clonotypes is critical for the expansion of tumor-reactive NY-ESO-1-specific CD8+ T cells following peptide-based vaccine strategies.