HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice

  • Authors:
    • Yutaka Motomura
    • Yoshiaki Ikuta
    • Toshimitsu Kuronuma
    • Hiroyuki Komori
    • Masaaki Ito
    • Masami Tsuchihara
    • Yoshiyuki Tsunoda
    • Hirofumi Shirakawa
    • Hideo Baba
    • Yasuharu Nishimura
    • Taira Kinoshita
    • Tetsuya Nakatsura
  • Corresponding author:
  • View Affiliations

  • Published online on: Thursday, May 1, 2008
  • Pages: 985-990 DOI: 10.3892/ijo.32.5.985

Abstract

We previously reported that glypican-3 (GPC3) is uniquely overexpressed in human hepatocellular carcinoma and melanoma and that it is an ideal tumor antigen for immunotherapy in mouse models. We recently identified both HLA-A24 (A*2402) and H-2Kd-restricted GPC3298-306 (EYILSLEEL) and HLA-A2 (A*0201)-restricted GPC3144-152 (FVGEFFTDV), both of which can induce GPC3-reactive cytotoxic T cells (CTLs). The present study was a preclinical study in a mouse model that was conducted in order to design an optimal schedule for clinical trial of GPC3-derived peptide vaccine. When BALB/c mice were intradermally vaccinated at the base of the tail with Kd-restricted GPC3298-306 peptide mixed with incomplete Freund's adjuvant (IFA), the peptide-specific CTLs were induced. But the peptide alone could not induce peptide-specific CD8+ T cells. Furthermore, proteomic analyses showed that IFA protected the peptide against degradation in the human serum. Peptide-reactive CTLs were induced by peptide vaccine in a dose-dependent manner. In addition, at least two vaccinations with a single dose >10 µg were needed for the induction of GPC3298-306-specific CTLs. But repeated vaccination with a lower dose of GPC3298-306 did not induce peptide-specific CTLs. Similarly, induction of an Ag-specific immune response by HLA-A2 GPC3144-152 depended on the dose administered. The results of this study suggested that IFA is one of the indispensable adjuvants for peptide-based immunotherapy, and that the immunological effect of peptide vaccines depends on the dose of peptide injected.
Journal Cover

May 2008
Volume 32 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
2014 I.F. (Expected) ≥ 3.310 Ranked #30/202 Oncology
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APA
Motomura, Y., Ikuta, Y., Kuronuma, T., Komori, H., Ito, M., Tsuchihara, M. ... Nakatsura, T. (2008). HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice. International Journal of Oncology, 32, 985-990. http://dx.doi.org/10.3892/ijo.32.5.985
MLA
Motomura, Y., Ikuta, Y., Kuronuma, T., Komori, H., Ito, M., Tsuchihara, M., Tsunoda, Y., Shirakawa, H., Baba, H., Nishimura, Y., Kinoshita, T., Nakatsura, T."HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice". International Journal of Oncology 32.5 (2008): 985-990.
Chicago
Motomura, Y., Ikuta, Y., Kuronuma, T., Komori, H., Ito, M., Tsuchihara, M., Tsunoda, Y., Shirakawa, H., Baba, H., Nishimura, Y., Kinoshita, T., Nakatsura, T."HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice". International Journal of Oncology 32, no. 5 (2008): 985-990. http://dx.doi.org/10.3892/ijo.32.5.985