局部放疗通过增强抗原交叉提呈和 T 细胞浸润提高全身 CAR-T 细胞疗效

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas.

However, a significant portion of patients either relapse or fail to respond.

Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy.

We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects on tumor growth in irradiated masses.

Notably, a significant additional increase in antitumor effect was observed in nonirradiated tumors.

Mechanistically, our results validate activation of the cyclic guanosine adenosine synthetase/stimulator of interferon genes pathway, tumor-associated antigen crosspriming, and elicitation of epitope spreading. Collectively, our findings suggest that RT may serve as an optimal priming and bridging modality for CAR T-cell therapy, overcoming treatment resistance and improving clinical outcomes in patients with CD19+ hematologic malignancies.