The Art and Science of Selecting a CD123-Specific Chimeric Antigen Receptor for Clinical Testing

The Art and Science of Selecting a CD123-Specific Chimeric Antigen Receptor for Clinical Testing

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Chimeric antigen receptor (CAR) T cells targeting CD123, an acute myeloid leukemia (AML) antigen, hold the promise of improving outcomes for patients with refractory/recurrent disease.We generated five lentiviral vectors encoding CD20, which may serve as a target for CAR T cell depletion, and truvisionhealthftp.com 2nd or 3rd generation CD123-CARs since the benefit of two costimulatory domains is model dependent.Four CARs were based on the CD123-specific single-chain variable fragment (scFv) 26292 (292) and one CAR on the CD123-specific scFv 26716 (716), respectively.

We designed CARs with different hinge/transmembrane (H/TM) domains and costimulatory domains, in combination with the zeta (z) signaling domain: 292.CD8aH/TM.41BBz (8.

41BBz), 292.CD8aH/TM.CD28z (8.

28z), 716.CD8aH/TM.CD28z (716.

8.28z), 292.CD28H/TM.

CD28z (28.28z), and 292.CD28H/TM.

CD28.41BBz (28.28.

41BBz).Transduction efficiency, expansion, phenotype, and target cell recognition of the read more generated CD123-CAR T cells did not significantly differ.CAR constructs were eliminated for the following reasons: (1) 8.

41BBz CARs induced significant baseline signaling, (2) 716.8.28z CAR T cells had decreased anti-AML activity, and (3) CD28.

41BBz CAR T cells had no improved effector function in comparison to CD28z CAR T cells.We selected the 28.28z CAR since CAR expression on the cell surface of transduced T cells was higher in comparison to 8.

28z CARs.The clinical study (NCT04318678) evaluating 28.28z CAR T cells is now open for patient accrual.