Preclinical development of anti-CD21 chimeric antigen receptor T cells to treat T cell acute lymphoblastic leukemia.

ABSTRACT: Patients with relapsed/refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) have a dismal prognosis, highlighting the urgent need for effective therapies. Chimeric antigen receptor (CAR)-T cell approaches targeting pan-T cell antigens may be limited by T cell aplasia and fratricide, necessitating "rescue" allogeneic hematopoietic stem cell transplantation. In this study, we identify CD21, a pan-B cell marker, as a promising target for T-ALL immunotherapy. CD21 is expressed in 50% of T-ALL cases at diagnosis but in fewer than 10% of mature T cells. We observed that CAR-T cells targeting membrane-distal CD21 epitopes were ineffective, likely because of the bulky, glycosylated nature of the antigen. However, when we engineered CAR-T cells to target membrane-proximal CD21 epitopes usin

SUBMITTER: Maciocia N 

PROVIDER: S-EPMC7617635 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature