Dual-Specific CAR T Cell Expansion Improves Efficacy Against Solid Tumors in Mice

Evgin L, Kottke T, Tonne J, et al. Oncolytic Virus-Mediated Expansion of Dual-Specific CAR T Cells Improves Efficacy Against Solid Tumors in Mice. Science Translational Medicine. 2022; 14 (640) (doi: 10.1126/scitranslmed.abn2231).

Chimeric antigen receptor (CAR) T cell therapy alone has a suboptimal effect against solid tumors, largely owing to the absence of tumor-specific antigens, but pairing CAR treatment with oncolytic viruses may increase its clinical value in this setting. The research used murine models of melanoma and glioma. Dual-specific CAR T cells were preloaded with oncolytic vesicular stomatitis virus or with reovirus. Investigators observed that stimulation of the native T cell receptor with viral or virally encoded epitopes promoted greater proliferation, CAR-driven antitumor activity, and distinct memory phenotypes. By restimulating memory CAR T cells with viral T cell receptor specificity, the approach increased overall survival of mice with subcutaneous melanoma and intracranial glioma tumors. The findings have positive implications for human patients with solid tumors, according to the researchers.

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