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

Yoshihiro Tokunaga, Takahiro Sasaki, Shunsuke Goto, Keishi Adachi, Yukimi Sakoda, Koji Tamada

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)138-148
Number of pages11
JournalMolecular cancer therapeutics
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Enhanced Antitumor Responses of Tumor Antigen-Specific TCR T Cells Genetically Engineered to Produce IL7 and CCL19'. Together they form a unique fingerprint.

Cite this