PT  - JOURNAL ARTICLE
AU  - Komori, Hiroyuki
AU  - Nakatsura, Tetsuya
AU  - Senju, Satoru
AU  - Yoshitake, Yoshihiro
AU  - Motomura, Yutaka
AU  - Ikuta, Yoshiaki
AU  - Fukuma, Daiki
AU  - Yokomine, Kazunori
AU  - Harao, Michiko
AU  - Beppu, Toru
AU  - Matsui, Masanori
AU  - Torigoe, Toshihiko
AU  - Sato, Noriyuki
AU  - Baba, Hideo
AU  - Nishimura, Yasuharu
TI  - Identification of HLA-A2- or HLA-A24-Restricted CTL Epitopes Possibly Useful for Glypican-3-Specific Immunotherapy of Hepatocellular Carcinoma
AID  - 10.1158/1078-0432.CCR-05-2267
DP  - 2006 May 01
TA  - Clinical Cancer Research
PG  - 2689--2697
VI  - 12
IP  - 9
4099  - http://clincancerres.aacrjournals.org/content/12/9/2689.short
4100  - http://clincancerres.aacrjournals.org/content/12/9/2689.full
SO  - Clin Cancer Res2006 May 01; 12
AB  - Purpose and Experimental Design: We previously reported that glypican-3 (GPC3) was overexpressed, specifically in hepatocellular carcinoma (HCC) and melanoma in humans, and it was useful as a novel tumor marker. We also reported that the preimmunization of BALB/c mice with dendritic cells pulsed with the H-2Kd-restricted mouse GPC3298-306 (EYILSLEEL) peptide prevented the growth of tumor-expressing mouse GPC3. Because of similarities in the peptide binding motifs between H-2Kd and HLA-A24 (A*2402), the GPC3298-306 peptide therefore seemed to be useful for the immunotherapy of HLA-A24+ patients with HCC and melanoma. In this report, we investigated whether the GPC3298-306 peptide could induce GPC3-reactive CTLs from the peripheral blood mononuclear cells (PBMC) of HLA-A24 (A*2402)+ HCC patients. In addition, we used HLA-A2.1 (HHD) transgenic mice to identify the HLA-A2 (A*0201)–restricted GPC3 epitopes to expand the applications of GPC3-based immunotherapy to the HLA-A2+ HCC patients. Results: We found that the GPC3144-152 (FVGEFFTDV) peptide could induce peptide-reactive CTLs in HLA-A2.1 (HHD) transgenic mice without inducing autoimmunity. In five out of eight HLA-A2+ GPC3+ HCC patients, the GPC3144-152 peptide-reactive CTLs were generated from PBMCs by in vitro stimulation with the peptide and the GPC3298-306 peptide-reactive CTLs were also generated from PBMCs in four of six HLA-A24+ GPC3+ HCC patients. The inoculation of these CTLs reduced the human HCC tumor mass implanted into nonobese diabetic/severe combined immunodeficiency mice. Conclusion: Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for a large number of HCC patients.