Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients
Open accessAbstract
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.
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Patients with advanced stage HCC are more refractory to GPC3-targeted immunotherapies.
“patients with advanced stage HCC are more refractory to these treatments62,64,65,97,98.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [64]
The Introduction (page unavailable) mentions a GPC3-vaccine trial in advanced HCC and reports tumor lysis, but does not compare treatment resistance by disease stage. The Results and Discussion (page unavailable) describe limited effects on recurrence after curative treatment, not greater refractoriness in advanced HCC. Searches for advanced-stage resistance and stage-specific vaccine response found no such comparison. (LLM, conf=0.76)
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- Authors
- Sawada, Y., Yoshikawa, T., Ofuji, K., Yoshimura, M., Tsuchiya, N., Takahashi, M., Nobuoka, D., Gotohda, N., Takahashi, S., Kato, Y., Konishi, M., Kinoshita, T., Ikeda, M., Nakachi, K., Yamazaki, N., Mizuno, S., Takayama, T., Yamao, K., Uesaka, K., Furuse, J., Endo, I., & Nakatsura, T.
- Affiliations
- National Cancer Center Hospital East (JP)
- Okayama University (JP)
- National Cancer Center Hospital (JP)
- Nihon University (JP)
- Aichi Cancer Center (JP)
- Shizuoka Cancer Center (JP)
- Kyorin University (JP)
- Yokohama City University (JP)
- Corresponding author
- Nakatsura, Tetsuya
- ORCID
- Sawada, Yu
- Yoshikawa, Toshiaki
- Ofuji, Kazuya
- Tsuchiya, Nobuhiro
- Takahashi, Mari
- Nobuoka, Daisuke
- Gotohda, Naoto
- Takahashi, Shinichiro
- Kato, Yuichiro
- Konishi, Masaru
- Ikeda, Masafumi
- Nakachi, Kohei
- Yamazaki, Naoya
- Mizuno, Shoichi
- Takayama, Tadatoshi
- Yamao, Kenji
- Uesaka, Katsuhiko
- Furuse, Junji
- Endo, Itaru
- Nakatsura, Tetsuya
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2016-01-19
- Volume
- 5
- Issue
- 5
- Pages
- e1129483
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC4910752
- OpenAlex
- W2413809012
- Cited by
- 178
- References
- 0
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 15 · 2023: 18 · 2022: 14 · 2021: 19 · 2020: 20 · 2019: 26 · 2018: 14 · 2017: 18 · 2016: 4
- FWCI
- 14.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoImmunology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Narodowe Centrum Badań i Rozwoju
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- hepatocellular carcinoma, glypican-3, adjuvant therapy, tumor recurrence, surgical resection, radiofrequency ablation, tumor markers, cancer immunotherapy
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