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Cited by 302Immunotherapy and Immune ResponsesHepatocellular Carcinoma Treatment and PrognosisCancer Immunotherapy and Biomarkers

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Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival

Sawada, Yu, Yoshikawa, Toshiaki, Nobuoka, Daisuke, Shirakawa, Hirofumi, Kuronuma, Toshimitsu, Motomura, Yutaka, Mizuno, Shoichi, Ishii, Hiroshi, Nakachi, Kohei, Konishi, Masaru, Nakagohri, Toshio, Takahashi, Shinichiro, Gotohda, Naoto, Takayama, Tadatoshi, Yamao, Kenji, Uesaka, Katsuhiko, Furuse, Junji, Kinoshita, Taira, Nakatsura, Tetsuya·2012·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-11-3044

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Abstract

Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC. Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-γ ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS). Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers α-fetoprotein and/or des-γ-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N = 15) than in those with low frequencies (N = 18; P = 0.033). Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination. Clin Cancer Res; 18(13); 3686–96. ©2012 AACR.

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Metadata

Authors
Sawada, Y., Yoshikawa, T., Nobuoka, D., Shirakawa, H., Kuronuma, T., Motomura, Y., Mizuno, S., Ishii, H., Nakachi, K., Konishi, M., Nakagohri, T., Takahashi, S., Gotohda, N., Takayama, T., Yamao, K., Uesaka, K., Furuse, J., Kinoshita, T., & Nakatsura, T.
Affiliations
  • Nihon University (JP)
  • Authors' Affiliations: 1Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, Divisions of 2Surgery and 3Hepatobiliary & Pancreatic Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; 4Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo; 5Department of Gastroenterology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya; and 6Department of Digestive Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2012-07-01
Volume
18
Issue
13
Pages
3686-3696
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-11-3044
OpenAlex
W2132286877
Cited by
302
References
1
Citations by year
2026: 10 · 2025: 22 · 2024: 13 · 2023: 23 · 2022: 19 · 2021: 23 · 2020: 27 · 2019: 27 · 2018: 14 · 2017: 28 · 2016: 14 · 2015: 26 · 2014: 22 · 2013: 28 · 2012: 5
FWCI
11.33
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
glypican-3, peptide vaccine, hepatocellular carcinoma, cancer immunotherapy, CTL response, overall survival, predictive biomarkers, tumor-specific immunity, alpha-fetoprotein, PIVKA-II, vaccine safety, dose escalation
MeSH terms
Adult, Aged, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, T-Lymphocytes, Cytotoxic, Treatment Outcome, Cancer Vaccines, Kaplan-Meier Estimate, Glypicans

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