SECTM1-based CAR-T cells enriched with CD7low/negative subsets exhibit efficacy in CD7-positive malignancies.

CD7 has been found to be a promising chimeric antigen receptor (CAR)-T cell target in several clinical trials. However, its expression on normal T cells poses additional challenges in CD7-directed CAR, such as complete fratricide, contamination with malignant cells, and immune suppression due to T-cell aplasia. By taking advantage of evolved affinity between ligand and receptor, we constructed a CD7-directed CAR with the extracellular domain of SECTM1, a natural ligand of CD7, as the recognition domain. SECTM1 CAR-T cells killed the majority of T cells with high CD7 expression in vitro. However, SECTM1 CAR-T cells with low or negative CD7 expression survived, expanded, and showed strong cytotoxicity to CD7-positive malignant cell lines and primary leukemic blasts from T-ALL and AML patients in vitro. It also exhibited efficacy in inhibiting xenograft tumor growth in vivo. More exploration is needed for clinical efficacy potential to CD7 positive patients.