Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican3derived peptide

Yoshitaka Tada, Toshiaki Yoshikawa, Manami Shimomura, Yu Sawada, Mayuko Sakai, Hirofumi Shirakawa, Daisuke Nobuoka, Tetsuya Nakatsura

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Glypican-3 (GPC3), which is a carcinoembryonic antigen, is overexpressed in human hepatocellular carcinoma (HCC). Previously, we performed a phase I clinical trial of GPC3derived peptide vaccination in patients with advanced HCC, and reported that GPC3 peptide vaccination is safe and has clinical efficacy. Moreover, we proposed that a peptide specific CTL response is a predictive marker of overall survival in patients with HCC who receive peptide vaccination. In this study, we established GPC3 derived peptide specific CTL clones from the PBMCs of an HLAA02:07 positive patient with HCC who was vaccinated with an HLA A2restricted GPC3 peptide vaccine and showed a clinical response in the phase I clinical trial. Established CTL clones were analyzed using the IFN ELISPOT assay and a cytotoxicity assay. GPC3 peptide specific CTL clones were established successfully from the PBMCs of the patient. One CTL clone showed cytotoxicity against cancer cell lines that expressed endogenously the GPC3 peptide. The results suggest that CTLs have high avidity, and that natural antigen specific killing activity against tumor cells can be induced in a patient with HCC who shows a clinical response to vaccination with the GPC3144-152 peptide.

Original languageEnglish
Pages (from-to)1019-1026
Number of pages8
JournalInternational Journal of Oncology
Volume43
Issue number4
DOIs
Publication statusPublished - Oct 2013
Externally publishedYes

Fingerprint

Glypicans
Cytotoxic T-Lymphocytes
Hepatocellular Carcinoma
Vaccination
Peptides
Clone Cells
Clinical Trials, Phase I
Enzyme-Linked Immunospot Assay
Subunit Vaccines
Carcinoembryonic Antigen
Neoplasms
Antigens
Cell Line
Survival

Keywords

  • CTL clone
  • Glypican3
  • Peptide vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican3derived peptide. / Tada, Yoshitaka; Yoshikawa, Toshiaki; Shimomura, Manami; Sawada, Yu; Sakai, Mayuko; Shirakawa, Hirofumi; Nobuoka, Daisuke; Nakatsura, Tetsuya.

In: International Journal of Oncology, Vol. 43, No. 4, 10.2013, p. 1019-1026.

Research output: Contribution to journalArticle

Tada, Yoshitaka ; Yoshikawa, Toshiaki ; Shimomura, Manami ; Sawada, Yu ; Sakai, Mayuko ; Shirakawa, Hirofumi ; Nobuoka, Daisuke ; Nakatsura, Tetsuya. / Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican3derived peptide. In: International Journal of Oncology. 2013 ; Vol. 43, No. 4. pp. 1019-1026.
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