PD-L1-armored CD19/CD22 dual-targeted CAR-T cell co-infusion bridging to allogeneic hematopoietic stem cell transplantation achieves 7-year sustained remission in an adult patient with early relapsed, chemorefractory B-cell acute lymphoblastic leukemia: a case report

BackgroundAntigen escape and PD-L1/PD-1 axis-mediated immunosuppression in the tumor microenvironment (TME) are the predominant drivers of treatment failure in adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). CD19-targeted CAR-T monotherapy has limited ability to overcome these two core resistance mechanisms, and achieving long-term durable remission remains a critical unmet clinical need in adults with high-risk, chemorefractory B-ALL.MethodsThis is a single-center, retrospective case report of an adult patient with early-relapsed, chemorefractory B-ALL.

Two independent CAR-T products were manufactured from the patient’s autologous peripheral blood mononuclear cells (PBMCs): (1) CD19 CAR-T cells containing an anti-CD19 single-chain variable fragment (scFv), a CD28 transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ signaling domain; (2) PD-L1-armored CD22 CAR-T cells containing an anti-CD22 scFv, a CD8 transmembrane domain, a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and a membrane-tethered anti-PD-L1 scFv for spatially restricted immune checkpoint modulation. The two CAR-T products were co-infused at doses of 5.0×105 cells/kg (CD19 CAR-T) and 3.1×105 cells/kg (PD-L1-armored CD22 CAR-T), respectively.