Researchers at St. Jude remade an anti-CD33 chimeric antigen receptor (CAR) that incorporates a 4-1BB-CD3ζ signaling tail previously proven effective in clinical trials. This CAR targets CD33 even at effector to target (E:T) ratios of less than one, which may allow for clinical potency even in the setting of high tumor burden. Treatment with specific inhibitors during ex vivo CAR T cell expansion modulated the differentiation program of CAR T cells, preserving a less differentiated phenotype, and improved in vivo persistence without disruption of normal ex vivo proliferation. It therefore, can be incorporated into CAR T cell production regimens without impacting yield. This is important as the inability to produce adequate CAR T cell numbers for treatment remains a significant limitation.
Granted Patents or Published Applications
Related Scientific References
Zheng W, O'Hear CE, Alli R, Basham JH, Abdelsamed HA, Palmer LE, Jones LL, Youngblood B, Geiger TL. “PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells.” Leukemia. 2018 May;32(5):1157-1167. doi: 10.1038/s41375-017-0008-6. Epub 2018 Feb 2.
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