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Assessing Ionizing Radiation as a Strategy to Improve CAR T-Cell Tumor Infiltration

Zhan L, Clark MA, Loos P Ionizing Radiation Enhances CAR T-Cell Infiltration and Efficacy in Solid Tumors. Frontiers in Immunology. 2026; (doi: 10.3389/fimmu.2026.1704419).

Irradiating tumors before administering chimeric antigen receptor (CAR) T-cell therapy may boost CAR T-cell infiltration and improve efficacy in solid tumors, researchers report. Unaccommodating aspects of the solid tumor microenvironment — such as a poorly functioning vasculature and limited blood flow that inhibits CAR T-cell infiltration, persistence, and antitumor activity — have largely limited CAR T-cell therapy's application in this setting. However, investigators theorized that pretreatment with ionizing radiation (IR) might temporarily improve vascular perfusion and enhance CAR T-cell delivery and therapeutic performance. In a mouse model of melanoma, they found that a single 8-Gy dose of IR, delivered to tumors 4 hours before systemic introduction of CAR T-cell infusion, resulted in greater intratumoral CAR T-cell accumulation compared with non-irradiated tumors. The strategy also significantly slowed tumor progression and increased survival relative to radiation alone or CAR T cells alone.

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