Development of glypican-3-targeted cancer immunotherapy

Toshiaki Yoshikawa, Yu Sawada, Mayuko Yoshimura, Kazuya Ofuji, Tetsuya Nakatsura

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Glypican-3 (GPC3) is an onco-fetal antigen expressed in the placenta and embryonic liver and over-expressed in human hepatocellular carcinoma (HCC). We found that GPC3 is useful both as a novel tumor marker and as a target antigen for immunotherapy in several mouse studies. We identified human leukocyte antigen (HLA)-A24-restricted GPC3 298–306 (EYILSLEEL) and HLA-A2-restricted GPC3 144–152 (FVGEFFTDV) peptides that can induce GPC3-reactive cytotoxic T lymphocytes (CTLs). Based on results obtained from preclinical mouse studies, we conducted a phase I clinical trial using a GPC3-derived peptide vaccine. Results showed that the GPC3-derived peptide vaccine was well-tolerated. Furthermore, this is the first study to show that the frequency of peptide-specific CTLs correlated with overall survival in patients with HCC receiving peptide vaccines. Next, we conducted a phase II clinical trial of the GPC3-derived peptide vaccine as an adjuvant therapy for patients with HCC after surgery or radiofrequency ablation. We are now initiating a pilot study of liver biopsies from patients with advanced HCC before and after GPC3 peptide vaccination. In addition, we investigated whether GPC3-based immunotherapy can be applied to other GPC3-expressing cancers, such as clear cell carcinoma of the ovary and pediatric cancers, and are initiating clinical trials to further these studies. We expect that the results of these trials will provide the rationale for a larger clinical trial to determine the efficacy of the GPC3- derived peptide vaccine and to advance future drug development using this approach.

Original languageEnglish
Title of host publicationInflammation and Immunity in Cancer
PublisherSpringer Japan
Pages133-143
Number of pages11
ISBN (Electronic)9784431553274
ISBN (Print)9784431553267
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Keywords

  • Clinical trial
  • Cytotoxic T lymphocyte
  • Glypican-3
  • Peptide vaccine

ASJC Scopus subject areas

  • General Medicine
  • General Immunology and Microbiology

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