期刊
JOURNAL OF IMMUNOTHERAPY
卷 31, 期 8, 页码 781-791出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e318183af0b
关键词
cancer vaccines; analog peptides; CpG; melanoma
资金
- Clinical Trial Grant/Melanoma Initiative from the Cancer Research Institute
- National Institutes of Health
- National Cancer Institute [CA90360, CA112198]
Analog peptides represent a promising tool to further optimize peptide-based vaccines in promoting the expansion of tumor antigen-specific cytotoxic T lymphocytes. Here, we report the results of a pilot trial designed to study the immunogenicity of the analog peptide NY-ESO-1157-165V 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, 3 patients); Montanide and peptide NY-ESO-1 157-165V (arm 2, 2 patients) or with Montanide, CpG, and peptide NY-ESO-1 157-165V farm 3, 3 patients). Only the 3 patients immunized with Montanide, CpG, and peptide NY-ESO-1 157-165V in arm 3 developed a rapid increase of effector-memory NY-ESO1-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 2 patients with advanced disease, but failed to prime tumor-reactive NY-ESO-1-specific T cells in I patient with no spontaneously tumor-induced CD8(+) T-cell responses to NY-ESO-1. Collectively, our data support the capability of the analog 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 after-peptide-based vaccine strategies.
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