Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response.

ABSTRACT: Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering β-emitting ¹⁷⁷Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of ¹⁷⁷Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumor

SUBMITTER: Yang Y 

PROVIDER: S-EPMC10972862 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature