Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma

• Published in: Oncoimmunology Vol. 6; no. 10; p. e1346764
• Main Authors: Tsuchiya, Nobuhiro, Yoshikawa, Toshiaki, Fujinami, Norihiro, Saito, Keigo, Mizuno, Shoichi, Sawada, Yu, Endo, Itaru, Nakatsura, Tetsuya
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.10.2017; Taylor & Francis Group
• Subjects: CTL; Glypican-3 (GPC3); HCC; immunological efficacy; Original Research; Peptide vaccine; HCC; CTL; Glypican-3 (GPC3); Peptide vaccine; immunological efficacy
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2017.1346764

We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination. The secondary endpoints were clinical and biologic outcomes. We demonstrated that the present vaccine induced GPC3 peptide-specific cytotoxic T lymphocytes (CTLs), which were found to infiltrate into the tumor. Moreover, we established GPC3 peptide-specific CTL clones from a biopsy specimen: these cells exhibited GPC3 peptide-specific cytokine secretion and cell cytotoxicity. The plasma GPC3 level tended to decrease temporarily at least once during the follow-up period. The GPC3-specific CTL frequency after vaccination was correlated with overall survival. The degree of skin reactions at the injection site correlated with the GPC3 peptide-specific CTLs. Furthermore, we sequenced the T cell receptors (TCRs) of tumor-infiltrating lymphocyte (TIL) clones, and confirmed the existence of this TCR repertoire in both tumor tissue and PBMCs. In response to these data, we are developing TCR-engineered T cell therapy using TCR sequences obtained from GPC3 peptide-specific CTL clones for improved efficacy in patients with advanced HCC.