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. 2016 Jan 19;5(5):e1129483.
doi: 10.1080/2162402X.2015.1129483. eCollection 2016 May.

Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients

Yu Sawada  1 , Toshiaki Yoshikawa  2 , Kazuya Ofuji  2 , Mayuko Yoshimura  2 , Nobuhiro Tsuchiya  1 , Mari Takahashi  2 , Daisuke Nobuoka  3 , Naoto Gotohda  4 , Shinichiro Takahashi  4 , Yuichiro Kato  4 , Masaru Konishi  4 , Taira Kinoshita  5 , Masafumi Ikeda  6 , Kohei Nakachi  6 , Naoya Yamazaki  7 , Shoichi Mizuno  2 , Tadatoshi Takayama  8 , Kenji Yamao  9 , Katsuhiko Uesaka  10 , Junji Furuse  11 , Itaru Endo  12 , Tetsuya Nakatsura  2
Affiliations

Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients

Yu Sawada et al. Oncoimmunology. .

Abstract

The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. 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 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.

Keywords: Adjuvant therapy; CTL; HCC; glypican-3; peptide vaccine.

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Figures

Figure 1.
Figure 1.
Trial profile.
Figure 2.
Figure 2.
Kaplan–Meier curves for recurrence-free survival and overall survival in 41 patients who received vaccinations in conjunction with surgery or radiofrequency ablation.
Figure 3.
Figure 3.
Cytotoxic T lymphocyte (CTL) analysis in peripheral blood mononuclear cells (PBMCs) and recurrent tumors. (A) Immunohistochemical staining for glypican-3 (GPC3) showed positivity in the primary tumor. The recurrent tumor appeared to lack GPC3 expression. Change in the expression of GPC3 in cases 42 and 53 after GPC3 peptide vaccination. Magnification = 200X. (B) Ex vivo interferonγ (IFNγ) ELISPOT assays for GPC3 in 5 × 105 peripheral blood mononuclear cells were performed before and after vaccination. Δ spot number indicates the number of GPC3-peptide-specific CTLs. The number of IFNγ-positive spots increased in the wells pre-incubated with GPC3 peptide.
Figure 4.
Figure 4.
Kaplan–Meier curves for recurrence-free and overall survival. (A) Thirty-five patients treated with surgery and vaccination did not have significantly longer recurrence-free survival or overall survival rates than the 33 patients who underwent surgery only. (B) Among patients with glypican-3 (GPC3)-positive tumors, the recurrence rate was significantly lower in the 25 patients treated with surgery and vaccination compared to the 21 patients who underwent surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The 25 patients treated with surgery and vaccination tended to have longer recurrence-free and overall survival rates compared to the 21 patients who underwent surgery only.
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