title: Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients.
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.
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ofuji
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Kita-ku, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nobuoka
authors.affiliation: Division of Surgery, National Cancer Center, Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Gotohda
authors.affiliation: Division of Surgery, National Cancer Center, Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Surgery, National Cancer Center, Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Surgery, National Cancer Center, Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Aichi Cancer Center Hospital , Chikusa-ku, Nagoya, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Division of Hepatobiliary & Pancreatic Medical Oncology, National Cancer Center Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Division of Hepatobiliary & Pancreatic Medical Oncology, National Cancer Center Hospital East , Kashiwa, Chiba, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.affiliation: Department of Dermatology, National Cancer Center Hospital , Chuo-ku, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Digestive Surgery, Nihon University School of Medicine , Itabashi-ku, Tokyo, Japan.
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital , Chikusa-ku, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital , Sunto- Nagaizumi, Shizuoka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Uesaka
authors.affiliation: Department of Medical Oncology, Kyorin University School of Medicine , Mitaka-shi, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine , Kanazawa-ku, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Kashiwa, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
keywords: Adjuvant therapy; CTL; HCC; glypican-3; peptide vaccine