Modified CD15/CD16-CLL1 inhibitory CAR-T cells for mitigating granulocytopenia toxicities in the treatment of acute myeloid leukemia.

ABSTRACT: CLL1 Chimeric antigen receptor T-cell (CAR-T) therapy, as a promising immunotherapeutic approach, has demonstrated its potential to enhance the prognosis of patients diagnosed with acute myeloid leukemia (AML). However, due to the overexpression of CLL1 on neutrophils, CAR-T cells not only eliminated tumor cells but also eradicated neutrophils simultaneously, resulting in severe granulocytopenia and subsequent infections. Considering the distinct expression levels of CD15/CD16 on neutrophils and AML blasts, we have devised novel modified CD15 /CD16-CLL1 iCAR structures incorporating diverse inhibitory elements. Through extensive screening of structural optimization, we have successfully identified CD16-CLL1 iCAR-T cells that combine PD1 and 2B4 blockade, as well as a single VHH fragment re

SUBMITTER: Zhang R 

PROVIDER: S-EPMC11667018 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature