論文

国際誌
2017年

Transfer of in vitro-expanded naïve T cells after lymphodepletion enhances antitumor immunity through the induction of polyclonal antitumor effector T cells.

PloS one
  • Tomohiro Tanaka
  • ,
  • Satoshi Watanabe
  • ,
  • Miho Takahashi
  • ,
  • Ko Sato
  • ,
  • Yu Saida
  • ,
  • Junko Baba
  • ,
  • Masashi Arita
  • ,
  • Miyuki Sato
  • ,
  • Aya Ohtsubo
  • ,
  • Satoshi Shoji
  • ,
  • Koichiro Nozaki
  • ,
  • Kosuke Ichikawa
  • ,
  • Rie Kondo
  • ,
  • Nobumasa Aoki
  • ,
  • Yasuyoshi Ohshima
  • ,
  • Takuro Sakagami
  • ,
  • Tetsuya Abe
  • ,
  • Hiroshi Moro
  • ,
  • Toshiyuki Koya
  • ,
  • Junta Tanaka
  • ,
  • Hiroshi Kagamu
  • ,
  • Hirohisa Yoshizawa
  • ,
  • Toshiaki Kikuchi

12
8
開始ページ
e0183976
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0183976

The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo-expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo-expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0183976
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28854279
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576657
ID情報
  • DOI : 10.1371/journal.pone.0183976
  • PubMed ID : 28854279
  • PubMed Central 記事ID : PMC5576657

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