論文

査読有り 国際誌
2022年1月

Enhanced Antitumor Responses of Tumor Antigen-Specific TCR T Cells Genetically Engineered to Produce IL7 and CCL19

Molecular Cancer Therapeutics
  • Yoshihiro Tokunaga
  • ,
  • Takahiro Sasaki
  • ,
  • Shunsuke Goto
  • ,
  • Keishi Adachi
  • ,
  • Yukimi Sakoda
  • ,
  • Koji Tamada

21
1
開始ページ
138
終了ページ
148
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1535-7163.mct-21-0400
出版者・発行元
American Association for Cancer Research (AACR)

Although adoptive transfer of T cells genetically engineered to express chimeric antigen receptor (CAR) or T-cell receptor (TCR) has been actively developed and applied into clinic recently, further improvement of these modalities is highly demanded, especially in terms of its efficacy. Because we previously revealed the profound enhancement of antitumor effects of CAR T cells by concomitant expression of IL7 and CCL19, this study further explored a potential of IL7/CCL19 production technology to augment antitumor effects of TCR T cells. IL7/CCL19-producing P1A tumor antigen-specific TCR T cells (7 × 19 P1A T cells) demonstrated significantly improved antitumor effects, compared with those without IL7/CCL19 production, and generated long-term memory responses. The antitumor effects of 7×19 P1A T cells were further upregulated by combination with anti-PD-1 antibody, in which blockade of PD-1 signal in both 7×19 P1A T cells and endogenous T cells plays an important role. Taken together, our study demonstrated that concomitant production of IL7 and CCL19 by genetically engineered tumor-reactive T cells could synergize with PD-1 blockade therapy to generate potent and long-lasting antitumor immunity.

リンク情報
DOI
https://doi.org/10.1158/1535-7163.mct-21-0400
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34675119
URL
https://syndication.highwire.org/content/doi/10.1158/1535-7163.MCT-21-0400
ID情報
  • DOI : 10.1158/1535-7163.mct-21-0400
  • ISSN : 1535-7163
  • eISSN : 1538-8514
  • PubMed ID : 34675119

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