低剂量 (125)I 照射增强 PRC1 靶向 NIS-CAR-T 细胞对乳腺癌细胞的细胞毒性

The efficacy of chimeric antigen receptor (CAR)-T therapy in solid tumors is limited by the immunosuppressive microenvironment and poor T-cell infiltration. Radiotherapy offers immunomodulatory potential, yet its synergy with CAR-T via targeted internal radionuclides remains unexplored.

Here, we identified protein regulator of cytokinesis 1 (PRC1) as a novel immunotherapeutic target. Through bioinformatic analysis, we engineered PRC1-specific CAR-T cells coexpressing the sodium iodide symporter (NIS) and an shRNA targeting SLC26A4, enabling enhanced iodide uptake and retention.

These NIS-CAR-T cells demonstrated potent, antigen-restricted cytotoxicity and cytokine secretion upon co-culture with breast cancer cells. Low-dose 125 I selectively induced cytolysis in tumor cells without impairing CAR-T function. At low effector-to-target ratios mimicking poorly infiltrated "cold" tumors, internal irradiation via 125 I significantly boosted CAR-T killing, even against low-antigen tumors.

This study introduces a multifunctional CAR-T platform that integrates internal radiotherapy to overcome key barriers in solid tumors, thereby offering a radiosensitized cellular therapy designed for the hostile tumor microenvironment.