Abstract CT115: Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients
Authors: Sawada Yu , Yoshikawa Toshiaki , Ofuji Kazuya , Yoshimura Mayuko , Tsuchiya Nobuhiro , Takahashi Mari , Nobuoka Daisuke , Mizuno Shoichi , Endo Itaru , Nakatsura Tetsuya 
Published: August 2015

Abstract
Background and purpose: In a phase I trial for advanced hepatocellular carcinoma (HCC), glypican-3(GPC3)-derived peptide vaccination was well-tolerated, and immune responses and antitumor efficacy were noted. The recurrence rates of HCC are still high and immunotherapy, as an adjuvant therapy, is expected. Therefore, we have conducted a phase II study of GPC3 peptide vaccine as an adjuvant therapy for HCC patients.
Study design: Forty one patients with initial HCC, who had undergone surgery or radiofrequency ablation (RFA), were analyzed in this phase II, open-label, single-arm trial.Ten vaccinations were performed for one year after curative treatment. The primary endpoints were 1- and 2-year recurrence rates. The secondary endpoints were safety and immune responses. We have evaluated GPC3-specific CTL response in PBMCs by IFN-γ enzyme-linked immunospot (ELISPOT) assay. We have evaluated the expression of GPC3 in the 33 primary tumors and 11 recurrence tumors, that could be obtained, by immunohistochemical analysis, and the phenotype of CTLs in recurrence tumor and vaccine site by flow cytometry.
Results: GPC3 peptide vaccine showed no severe adverse events. 1-year and 2-year recurrence rates of the 41 patients treated with the vaccination were 24.4% and 53.7%. In this study, 35 patients had received surgery and 6 patients RFA therapy. We analyzed the case-control study to evaluate the reduction in the risk of post-operative recurrence by vaccination. Thirty three patients with initial HCC who underwent curative resection in the same period were selected as control group. The recurrence rate tended to be lower in 35 patients treated with surgery and the vaccination than in 33 patients with surgery alone (28.6% and 54.3% vs 39.4% and 54.5% at 1 year and 2 year, p = 0.346, 0.983). In the patients with GPC3 positive tumor, the recurrence rate was significantly lower in 25 patients treated with surgery and the vaccination than in 21 patients with surgery alone (24% and 48% vs 52.4% and 61.9% at 1 year and 2 year, p = 0.047, 0.387), and there was no significant difference in clinical background. There were not the correlation between the relapse free survival and the antigen-specific immune response as measured by IFN-γ ELISPOT assay. Two of 11 case appeared to lack GPC3 expression in the recurrence tumor, although GPC3 was expressed in the primary HCC tissue before GPC3 peptide vaccine. In the other case, GPC3 peptide specific CTLs had infiltrated into recurrence tumor, and the expression of PD-1 among CD8 positive T cells, was higher in recurrence tumor and vaccine site than in PBMCs.
Conclusions: GPC3 peptide vaccine for patient with GPC3 positive tumor could improve 1-year recurrence rates. This study showed GPC3 expression of the primary tumor could be the biomarker for a larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.
Citation Format: Yu Sawada, Toshiaki Yoshikawa, Kazuya Ofuji, Mayuko Yoshimura, Nobuhiro Tsuchiya, Mari Takahashi, Daisuke Nobuoka, Shoichi Mizuno, Itaru Endo, Tetsuya Nakatsura. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT115. doi:10.1158/1538-7445.AM2015-CT115