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HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells
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HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells
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Journal Article
HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells
2011
Overview
Glypican‐3 (GPC3) is an onco‐fetal antigen that is overexpressed in human hepatocellular carcinoma (HCC), and is only expressed in the placenta and embryonic liver among normal tissues. Previously, we identified an HLA‐A2‐restricted GPC3144–152 (FVGEFFTDV) peptide that can induce GPC3‐reactive CTLs without inducing autoimmunity in HLA‐A2 transgenic mice. In this study, we carried out a phase I clinical trial of HLA‐A2‐restricted GPC3144–152 peptide vaccine in 14 patients with advanced HCC. Immunological responses were analyzed by ex vivoγ‐interferon enzyme‐linked immunospot assay. The frequency of GPC3144–152 peptide‐specific CTLs after vaccination (mean, 96; range, 5–441) was significantly larger than that before vaccination (mean, 6.5; range, 0–43) (P < 0.01). An increase in the GPC3144–152 peptide‐specific CTL frequency was observed in 12 (86%) of 14 patients after vaccination. Additionally, there was a significant correlation between the maximum value of GPC3144–152 peptide‐specific CTLs after vaccination and the dose of the peptide injected (P = 0.0166, r = 0.665). Moreover, we established several GPC3144–152 peptide‐specific CTL clones from PBMCs of patients vaccinated with GPC3144–152 peptide by single cell sorting using Dextramer and CD107a antibody. These CTL clones had high avidity (the recognition efficiency showing 50% cytotoxicity was 10−10 or 10−11 M) and could recognize HCC cell lines expressing GPC3 in an HLA‐class I‐restricted manner. These results suggest that GPC3144–152 peptide vaccine can induce high avidity CTLs capable of killing HCC cells expressing GPC3. This trial was registered with University Hospital Medical Information Network number 000001395. (Cancer Sci 2011; 102: 918–925)
Publisher
Blackwell Publishing Ltd,Blackwell
Subject
/ Biological and medical sciences
/ Cancer Vaccines - immunology
/ Cancer Vaccines - therapeutic use
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - pathology
/ Carcinoma, Hepatocellular - therapy
/ Cytotoxicity, Immunologic - immunology
/ Female
/ Humans
/ Liver Neoplasms - immunology
/ Male
/ Original
/ T-Lymphocytes, Cytotoxic - immunology
/ Tumors
