Immunization With Analog Peptide in Combination With CpG and Montanide Expands Tumor Antigen-specific CD8+ T Cells in Melanoma Patients

Abstract

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.

Analogue peptides for the immunotherapy of human acute myeloid leukemia

“…Similar modifications have led to peptide analogues which are effective at inducing immune responses against a range of tumor types including leukemia and solid tumors [54, [57][58][59]94,95](reviewed in [96]). Despite inherent problems in demonstrating the ability of modified peptides to recognize and kill tumor cells, some heteroclitic epitopes have shown promise in phase I clinical trials [18,71,97].…”

Spatiotemporal Regulation of Heat Shock Protein 90-Chaperoned Self-DNA and CpG-Oligodeoxynucleotide for Type I IFN Induction via Targeting to Static Early Endosome

“…Previous studies revealed that CpG-A or various DNAs needed to be retained for long periods in the endosomes of pDCs for sufficient activation of TLR9 signaling (25,26). Recently, CpG-ODNs have shown promising results as vaccine adjuvants for cancer immunotherapy due to their ability to induce potent Th1-type immune responses and anti-tumor responses (27)(28)(29)(30).…”

Efficient In vivo Priming by Vaccination with Recombinant NY-ESO-1 Protein and CpG in Antigen Naïve Prostate Cancer Patients

“…Patient F-9 even exhibited an ex vivo detectable T-cell response against NY-ESO-1 p157-165. Direct ex vivo antigen-specific T cells are rarely detected, but were found in several previously published studies either with NY-ESO-1 p157-165 peptide or Melan-A ELA-GIGILTV analog peptide when the vaccines were combined with Montanide and CpG (15,41,42). These studies indicate the important role of CpG as an adjuvant in peptide-based and recombinant protein vaccines.…”