17MB043 CAR-T: CAR-T Cells with Enhanced 41BB Co-Stimulation
Moffitt investigators developed a chimeric antigen receptor (CAR) with enhanced CD28 costimulatory regions. The typical CD28 domain increases T-cell activation, but this often leads to exhaustion and shortened persistence. The mutated CD28 domains have mutations that optimize CAR-T-cell function while preventing exhaustion and increasing persistence. The costimulatory regions have been tested in vivo in CD19 CAR-T constructs in mouse models with the findings that mice given CAR-T cells with only a mutated CD28 endodomain had a significant survival advantage, with 100% of mice alive after 62 days compared with 50% for mice with an unmutated endodomain. Ex vivo, the mutant CAR-T cells were found to be more sensitive to antigens, possess less exhaustion related transcription factors, and enhance PD-L1 stimulation.
PUBLICATION/PATENT
Provisional Patent filed for Dr. Davila
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