Direct comparison of in vivo fate of second and third-generation CD19-specific chimeric antigen receptor (CAR)-T cells in patients with b cell non-hodgkin lymphoma (B-NHL): Reversal of toxicity from tonic signaling

      Although 2nd-generation (2G) CD19-specific CARs containing CD28 or 4-1BB costimulatory endodomains (CE) show remarkable efficacy against B-NHL, the optimal choice of CEs in these and other CARs remains controversial. Individual CEs, such as CD28 may be associated with deleterious ligand-independent tonic signaling in the transduced T cell, but it is unclear if tonic 4-1BB signaling may have such consequences as well, and if such effects can be reversed.
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