2777 - Radiation Enhances the Efficacy of HER2.28?/PD-L1.BB CAR-T Cells Against Triple-Negative Breast Cancer By Increased the Infiltration of CD8+ T Cells into Tumors

Z. Benxia, N. Liu, Y. Chen, S. Pei, and W. Yongsheng; sichuan university, chengdu, sichuan, China

Purpose/Objective(s): Poor intratumoral infiltration is one of the most challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Radiotherapy (RT), especially hypofractionation radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Besides, the tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) highly expressed inhibitory markers and genes associated with functional exhaustion (e.g., PD-1, CTLA4, TIGIT, TIM-3). RT combined with CAR-T cells has been reported to improve the efficacy in clinical, but the combination strategy and timing needed to be clarified. Materials/

Methods: Here, we combined RT (10 Gy×1) with HER2.28?/PD-L1.BB CAR-T cells to treat TNBC. We have applied flow cytometry, Elisa, cytokine assay, RNA sequencing, and mouse models of solid cancers.
Results: The combination therapy resulted in an effectively enhanced the intratumoral infiltration and treatment efficacy of CAR-T cells. The efficacy of this strategy was independent of tumor radiosensitivity and lymphodepleting preconditioning. Flow cytometry analysis revealed that the combination therapy increased the infiltration of CD8+ T cells into tumors, and (RNA-seq) analysis showed a decreased PD-L1 expression in tumors. Cytokine profiling showed that this combination did not increase the risk of cytokine release syndrome (CRS).
Conclusion: Our study demonstrates that a single dose of 10Gy is promising for CAR-T cell therapy optimization in solid tumors.