論文

査読有り
2015年5月

Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer

CLINICAL CANCER RESEARCH
  • Shinichi Kageyama
  • Hiroaki Ikeda
  • Yoshihiro Miyahara
  • Naoko Imai
  • Mikiya Ishihara
  • Kanako Saito
  • Sahoko Sugino
  • Shugo Ueda
  • Takeshi Ishikawa
  • Satoshi Kokura
  • Hiroaki Naota
  • Kohshi Ohishi
  • Taizo Shiraishi
  • Naoki Inoue
  • Masashige Tanabe
  • Tomohide Kidokoro
  • Hirofumi Yoshioka
  • Daisuke Tomura
  • Ikuei Nukaya
  • Junichi Mineno
  • Kazutoh Takesako
  • Naoyuki Katayama
  • Hiroshi Shiku
  • 全て表示

21
10
開始ページ
2268
終了ページ
2277
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1078-0432.CCR-14-1559
出版者・発行元
AMER ASSOC CANCER RESEARCH

Purpose: Preparative lymphodepletion, the temporal ablation of theimmune system, has been reported to promote persistence of transferred cells along with increased rates of tumor regression in patients treated with adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy with T-cell receptor (TCR) gene-engineered T cells.
Experimental Design: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell transfer in patients with recurrent MAGE-A4-expressing esophageal cancer. The patients were given sequential MAGE-A4 peptide vaccinations. The regimen included neither lymphocyte-depleting conditioning nor administration of IL2. Ten patients, divided into 3 dose cohorts, received T-cell transfer.
Results: TCR-transduced cells were detected in the peripheral blood for 1 month at levels proportional to the dose administered, and in 5 patients they persisted for more than 5 months. The persisting cells maintained ex vivo antigen-specific tumor reactivity. Despite the long persistence of the transferred T cells, 7 patients exhibited tumor progression within 2 months after the treatment. Three patients who had minimal tumor lesions at baseline survived for more than 27 months.
Conclusions: These results suggest that TCR-engineered T cells created by relatively short-duration in vitro culture of polyclonal lymphocytes in peripheral blood retained the capacity to survive in a host. The discordance between T-cell survival and tumor regression suggests that multiple mechanisms underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy. (C)2015 AACR.

リンク情報
DOI
https://doi.org/10.1158/1078-0432.CCR-14-1559
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25855804
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000357335500014&DestApp=WOS_CPL
ID情報
  • DOI : 10.1158/1078-0432.CCR-14-1559
  • ISSN : 1078-0432
  • eISSN : 1557-3265
  • PubMed ID : 25855804
  • Web of Science ID : WOS:000357335500014

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