High expression of MAGE-A4 and MHC class I antigens in tumor cells and induction of MAGE-A4 immune responses are prognostic markers of CHP-MAGE-A4 cancer vaccine

Takuro Saito, Hisashi Wada, Makoto Yamasaki, Hiroshi Miyata, Hiroyoshi Nishikawa, Eiichi Sato, Shinichi Kageyama, Hiroshi Shiku, Masaki Mori, Yuichiro Doki

研究成果: Contribution to journalArticle査読

31 被引用数 (Scopus)

抄録

Purpose: We conducted a cancer vaccine clinical trial with MAGE-A4 protein. Safety, clinical response, and antigen-specific immune responses were analyzed and the prognostic factors by vaccination were investigated. Experimental design: Twenty patients with advanced esophageal, stomach or lung cancer were administered MAGE-A4 vaccine containing 300. μg protein subcutaneously once every 2 weeks in six doses. Primary endpoints of this study were safety and MAGE-A4 immune responses. Results: The vaccine was well tolerated. Fifteen of 20 patients completed one cycle of vaccination and two patients showed SD. A MAGE-A4-specific humoral immune response was observed in four patients who had high expression of MAGE-A4 and MHC class I on tumor cells. These four patients showed significantly longer overall survival than patients without an antibody response after vaccination (. p=. 0.009). Patients with tumor cells expressing high MAGE-A4 or MHC class I antigen showed significantly longer overall survival than those with low expression. Induction of CD4 and CD8T cell responses was observed in three and six patients, respectively, and patients with induction of MAGE-A4-specific IFNγ-producing CD8T cells, but not CD4T cells, lived longer than those without induction. Conclusions: The CHP-MAGE-A4 vaccine was safe. Expression of MAGE-A4 and MHC class I in tumor tissue and the induction of a MAGE-A4-specific immune response after vaccination would be feasible prognostic markers for patients vaccinated with MAGE-A4.

本文言語英語
ページ(範囲)5901-5907
ページ数7
ジャーナルVaccine
32
45
DOI
出版ステータス出版済み - 10 14 2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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