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Development of Glypican-3-Targeted Cancer Immunotherapy

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

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 GPC3298–306 (EYILSLEEL) and HLA-A2-restricted GPC3144–152 (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.

Keywords

Glypican-3 Peptide vaccine Clinical trial Cytotoxic T lymphocyte 

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Copyright information

© Springer Japan 2015

Authors and Affiliations

  • Toshiaki Yoshikawa
    • 1
  • Yu Sawada
    • 1
  • Mayuko Yoshimura
    • 1
  • Kazuya Ofuji
    • 1
  • Tetsuya Nakatsura
    • 1
  1. 1.Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan

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