CELL INTELLIGENCE · 肿瘤细胞治疗研究

Durable remissions after anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory B-lineage acute lymphoblastic leukaemia are limited by antigen escape and T-cell dysfunction. The tandem CAR22-19/LTG2737 construct links human-derived anti-CD22 and anti-CD19 scFvs to CD8 hinge/transmembrane, 4-1BB, and CD3ζ domains. In a multicentre phase I/II trial, all patients (n=11; 7 children, 4 adults) achieved complete remission by Day 28 (91% minimal residual disease-negative). At a 34-month median follow-up, median overall survival (OS) and leukaemia-free survival (LFS) were not reached. The 12-month OS was 82% (95%CI: 45%-95%) and LFS was 64% (95%CI: 30%-85%) without consolidative transplantation. Immune-effector cell-associated toxicities included cytokine release syndrome, haematotoxicity, and haemophagocytic lymphohistiocytosis-like syndrome. De novo CD19 escape caused one relapse. Exploratory multi-omic profiling linked durable response to higher CD22 antigen density on blasts; pre-infusion CD4 CAR-T cells expressing IL7Rα, LEF1, BACH2, and TCF7 but lower FOXP3; post-infusion NK-like effector CAR-T expansion; and central-memory CAR-T pool maintenance.