Last update 08 May 2025
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100 Clinical Results associated with GPC-3298306
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100 Translational Medicine associated with GPC-3298306
100 Patents (Medical) associated with GPC-3298306
1 Literatures (Medical) associated with GPC-3298306
International Journal of Oncology Q2 · MEDICINE
HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice
Q2 · MEDICINE
Article
Author: Komori, Hiroyuki ; Tsuchihara, Masami ; Nishimura, Yasuharu ; Baba, Hideo ; Kuronuma, Toshimitsu ; Motomura, Yutaka ; Shirakawa, Hirofumi ; Ikuta, Yoshiaki ; Nakatsura, Tetsuya ; Kinoshita, Taira ; Tsunoda, Yoshiyuki ; Ito, Masaaki
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 microg 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.
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