NIH Reporter #4UH3CA290241-03

CD28-KITv CAR T cells with PD-1 dominant negative receptor

This award supports the development of advanced CAR T-cell therapy for solid tumors using CD28-costimulated CARs, PD-1 dominant negative receptor checkpoint blockade, and c-KIT mutation co-stimulation, combined with targeted radiation therapy to enhance tumor infiltration and treatment efficacy.

Description

The project involves translating CD28-costimulated CARs targeting mesothelin, employing tumor-specific checkpoint blockade via PD1DNR, and utilizing a c-KIT mutation (KITv) as a co-stimulatory domain. The strategy includes non-ablative, tumor-targeted radiation therapy to promote tumor infiltration and systemic delivery of next-generation CAR T cells.

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