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Cited by 67Immunotherapy and Immune ResponsesHepatocellular Carcinoma Treatment and PrognosisCancer Immunotherapy and Biomarkers

Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma

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Tsuchiya, Nobuhiro, Yoshikawa, Toshiaki, Fujinami, Norihiro, Saito, Keigo, Mizuno, Shoichi, Sawada, Yu, Endo, Itaru, Nakatsura, Tetsuya·2017·OncoImmunology
DOI 10.1080/2162402x.2017.1346764PMC PMC5665076
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Abstract

We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination. The secondary endpoints were clinical and biologic outcomes. We demonstrated that the present vaccine induced GPC3 peptide-specific cytotoxic T lymphocytes (CTLs), which were found to infiltrate into the tumor. Moreover, we established GPC3 peptide-specific CTL clones from a biopsy specimen: these cells exhibited GPC3 peptide-specific cytokine secretion and cell cytotoxicity. The plasma GPC3 level tended to decrease temporarily at least once during the follow-up period. The GPC3-specific CTL frequency after vaccination was correlated with overall survival. The degree of skin reactions at the injection site correlated with the GPC3 peptide-specific CTLs. Furthermore, we sequenced the T cell receptors (TCRs) of tumor-infiltrating lymphocyte (TIL) clones, and confirmed the existence of this TCR repertoire in both tumor tissue and PBMCs. In response to these data, we are developing TCR-engineered T cell therapy using TCR sequences obtained from GPC3 peptide-specific CTL clones for improved efficacy in patients with advanced HCC.

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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 [62]

    The Discussion (page unavailable) says patients with advanced HCC who had not responded to sorafenib showed little clinical response to GPC3 peptide vaccination. The Results (Clinical responses; page unavailable) report progressive disease in 10 of 11 vaccinated patients. The paper does not establish that advanced-stage patients are more refractory than earlier-stage patients, or extend that finding to GPC3-targeted immunotherapies generally. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Tsuchiya, N., Yoshikawa, T., Fujinami, N., Saito, K., Mizuno, S., Sawada, Y., Endo, I., & Nakatsura, T.
Affiliations
  • National Cancer Center Exploratory Oncology Research & Clinical Trial Center (JP)
  • Yokohama City University (JP)
Corresponding author
Nakatsura, Tetsuya
ORCID
Venue
OncoImmunology
Publisher
Informa UK Limited
Published
2017-07-11
Volume
6
Issue
10
Pages
e1346764
ISSN
  • 2162-4011 (ISSN-L)
  • 2162-402X
DOI
10.1080/2162402x.2017.1346764
PMC
PMC5665076
OpenAlex
W2736137548
Cited by
67
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 2
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • OncoImmunology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Takeda Pharmaceutical Company
  • Narodowe Centrum Badań i Rozwoju
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, advanced liver cancer, cytotoxic T lymphocytes, tumor-infiltrating lymphocytes, T cell receptor repertoire, vaccine immunogenicity, overall survival

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