Efficacy-enhanced and cytokine release syndrome-attenuated anti-CD7 universal chimeric antigen receptor-T cell therapy for relapsed/refractory CD7-positive hematological malignancies: A phase I clinical study

Abstract Chimeric antigen receptor-T cell (CAR-T) therapy in T cell malignancies faces fratricide, T cell aplasia, and product contamination. Here, we successfully developed a universal anti-CD7 CAR-T product (RD13-01). RD13-01 contains a bbzg-CAR comprising an anti-CD7 single-chain variable fragment, a 4-1BB costimulatory domain, a CD3ζ signaling domain, the intracellular domain of the common γ chain, and a natural killer cell inhibitory molecule (E-cadherin). TRAC, CD7 and HLA-II were disrupted to avoid graft versus host disease (GvHD), fratricide and rejection. Bbzg-CAR-T exerted antitumor effects superior to those of conventional CAR-T, while exhibiting reduced cytokine production. Among 11 evaluable relapsed/refractory (r/r) patients, no dose-limited toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade≥3) occurred. Nine (82%) showed objective response. For r/r leukemia and NHL, complete response rates were 75% and 33.3% respectively. Outstanding safety and efficacy of this universal CAR-T product was achieved in CD7+ T cell malignancies.