GSE192453
Efficacy-enhanced anti-CD7 universal chimeric antigen receptor-T cell therapy for relapsed/refractory CD7-positive hematological malignancies: A phase I clinical study
Chimeric antigen receptor-T cell (CAR-T) therapy in T cell malignancies faces fratricide, T cell aplasia, and product contamination. We developed an universal anti-CD7 CAR-T cells in which TRAC, CD7 and HLA-II were disrupted, while E-cadherin (a NK cell inhibitory molecule) was introduced, to mitigate graft versus host disease (GvHD), fratricide and rejection. Furthermore, we designed a subtle receptor, bbzg-CAR, comprising not only conventional domains (anti-CD7 scFv, 4-1BB co-stimulatory domain, and CD3? signaling domain), but also the intracellular domain of common ? chain. Bbzg-CAR-T exerted anti-tumor effects superior to those of conventional universal CAR-T cells. In adoptive therapy for relapsed/refractory (r/r) patients, no dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade=3) was observed. Nine patients (82%) showed objective response with, complete response rates of 75% and 33.3% in r/r leukemia and lymphoma respectively. Preliminary safety and efficacy of this universal CAR-T product was achieved in CD7+ malignancies. Overall design: Single-cell RNA analysis were performed in RD13-01 product (batch number C20201001) and PBMCs from patient 5 at day 14 and day 19 post RD13-01 infusion.