CD7 CAR-T therapy: current developments, improvements, and dilemmas

Chimeric antigen receptor (CAR) T-cell therapy is an epoch-making immunotherapy for the treatment of relapsed or refractory (r/r) blood tumors, as demonstrated by its successful implementation in r/r B cell-derived malignancies. However, replicating this success in T-cell leukemia or lymphoma remains challenging. Among the various potential target antigens, CD7 has garnered attention as a promising candidate. CD7 CAR-T therapy is one of the most extensively studied approaches for treating r/r T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and r/r acute myeloid leukemia (AML). Based on the source of T cells, CAR-T products can be categorized as autologous and allogeneic, both of which are being tested in clinical trials, each offering specific advantages. Allogeneic CD7 CAR-T cells outperform autologous cells in terms of reducing manufacturing costs, ensuring consistent quality, and improving affordability and availability. Despite these advantages, challenges like graft-versus-host disease (GVHD), host-versus-graft reaction (HVGR), and fratricide pose significant barriers to the clinical application of allogeneic CD7 CAR-T cells. However, innovative gene-editing techniques, such as CRISPR/Cas9 and base editing, and more promising cell sources, such as natural killer T (NKT) cells and induced pluripotent stem cells (iPSCs), are emerging as potential solutions. In this review, we discuss the different categories of CD7 CAR-T products, their application in clinical settings, and directions for refinement.