TCR reserved and Power3 Gene Knock-out Allogeneic CD19-targeting CAR-T cell(Chinese PLA General Hospital)

The safety and efficacy of the chimeric antigen receptor (CAR)-T, a CD19-targeting, TRAC and Power3 double gene deleted allogeneic CAR-T cell product, are undergoing rigorous evaluation in NHL subjects from the ATHENA trial (NCT06014073). Unexpectedly, expansion of the initial residual CD3-positive CAR T from products were measured in patients' peripheral blood (PB) without exception. Accompanying with host immune reconstitution and appearance of the detectable B cells, the CD3-positive allogenic CAR T cells exhibited a compelling amplification advantage over CD3-negative CAR T cells. The amplification of CD3-positive CAR T cell population dynamically suppressed host B cell recovery, and presumably surveilled the recurrence or progression of tumors, but did not induce typical Graft-versus-host-disease (GvHD). Additionally, a series of in vitro experiments illustrated that the HLA-mismatched fratricide between host T cells and TCR-reserved Power3-deleted allogenic CAR T cells was markedly slashed, which in combination with investigators' observed clinical safety date supported the notion that only genomic deletion of Power3 gene in allo-CAR T cells is sufficient to overcome GvHD and host T cell-mediated rejection response.
In this study, investigators will disable the Power3 gene of T cells from healthy donors to prepare CAR T cells. This approach harnesses the tonic signaling of CAR T cells, resulting in enhanced persistence and improved response to treatment. The purpose of this study is to evaluate the safety and efficacy of allogeneic Power3 knock-out CD19 CAR-T in B-cell acute lymphoblastic leukaemia (B-ALL).