Enhanced anti-tumor responses of tumor antigen-specific TCR-T cells genetically engineered to produce IL-7 and CCL19.

While 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. Since we previously revealed the profound enhancement of anti-tumor effects of CAR-T cells by concomitant expression of interleukin (IL)-7 and CCL19, this study further explored a potential of IL-7/CCL19 production technology to augment anti-tumor effects of TCR-T cells. IL-7/CCL19-producing P1A tumor antigen-specific TCR-T cells (7×19 P1A-T cells) demonstrated significantly improved anti-tumor effects, compared to those without IL-7/CCL19 production, and generated long-term memory responses. The anti-tumor 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 IL-7 and CCL19 by genetically engineered tumor-reactive T cells could synergize with PD-1 blockade therapy to generate potent and long-lasting anti-tumor immunity.