Minibeam radiation therapy supports CAR T therapy in a rat model of CNS lymphoma

Radiotherapy is increasingly combined with CAR T cell therapy in B cell lymphomas, but treatment outcome may depend on the irradiation modality. We evaluated minibeam radiation therapy (MBRT) as a partner for CD19 CAR T cells in an orthotopic primary central nervous system (CNS) lymphoma model in immunodeficient rats. CAR T therapy prolonged survival compared with untreated controls. MBRT at 30 Gy followed by CAR T cells five days later produced the longest median survival among radiotherapy-containing regimens and improved outcome compared with conventional radiotherapy (CRT) based combinations. Histopathological findings were consistent with these survival differences. However, MBRT plus CAR T therapy did not significantly outperform CAR T monotherapy. These results indicate that MBRT provides a favorable, non-antagonistic radiotherapy context for CAR T therapy and suggest that radiation modality should be considered when designing combinations of radiotherapy with adoptive cellular therapies.