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.

中文翻译：

---

经基因工程改造以产生 IL7 和 CCL19 的肿瘤抗原特异性 TCR T 细胞的抗肿瘤反应增强

尽管基因工程表达嵌合抗原受体 (CAR) 或 T 细胞受体 (TCR) 的 T 细胞的过继转移已被积极开发并应用于临床，但迫切需要进一步改进这些方式，特别是在其功效方面。因为我们之前揭示了通过同时表达 IL7 和 CCL19 显着增强 CAR T 细胞的抗肿瘤作用，本研究进一步探索了 IL7/CCL19 生产技术增强 TCR T 细胞抗肿瘤作用的潜力。与不产生 IL7/CCL19 的细胞相比，产生 IL7/CCL19 的 P1A 肿瘤抗原特异性 TCR T 细胞（7 × 19 P1A T 细胞）显示出显着改善的抗肿瘤作用，并产生了长期记忆反应。7×19 P1A T细胞的抗肿瘤作用通过与抗PD-1抗体组合进一步上调，其中7×19 P1A T细胞和内源性T细胞中PD-1信号的阻断起重要作用。总之，我们的研究表明，基因工程肿瘤反应性 T 细胞同时产生 IL7 和 CCL19 可以与 PD-1 阻断疗法协同产生有效和持久的抗肿瘤免疫。