Open AccessHLA‐A2‐restricted glypican‐3 peptide‐specific CTL clones induced by peptide vaccine show high avidity and antigen‐specific killing activity against tumor cells
Author(s) -
Yoshikawa Toshiaki,
Nakatsugawa Munehide,
Suzuki Shiro,
Shirakawa Hirofumi,
Nobuoka Daisuke,
Sakemura Noriko,
Motomura Yutaka,
Tanaka Yukie,
Hayashi ShinIchi,
Nakatsura Tetsuya
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01896.x
Subject(s) - glypican 3 , avidity , ctl* , peptide vaccine , antigen , biology , immunology , cytotoxic t cell , peptide , epitope , virology , cd8 , in vitro , biochemistry , immunohistochemistry
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 GPC3 144–152 (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 GPC3 144–152 peptide vaccine in 14 patients with advanced HCC. Immunological responses were analyzed by ex vivo γ‐interferon enzyme‐linked immunospot assay. The frequency of GPC3 144–152 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 GPC3 144–152 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 GPC3 144–152 peptide‐specific CTLs after vaccination and the dose of the peptide injected ( P = 0.0166, r = 0.665). Moreover, we established several GPC3 144–152 peptide‐specific CTL clones from PBMCs of patients vaccinated with GPC3 144–152 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 GPC3 144–152 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 1395. ( Cancer Sci 2011; 102: 918–925)