The rational development of CD5-targeting biepitopic CARs with fully human heavy-chain-only antigen recognition domains.

ABSTRACT: T cell malignancies are a group of hematologic cancers with high recurrence and mortality rates. CD5 is highly expressed in ∼85% of T cell malignancies, although normal expression of CD5 is restricted to thymocytes, T cells, and B1 cells. However, CD5 expression on chimeric antigen receptor (CAR)-T cells leads to CAR-T cell fratricide. Once this limitation is overcome, CD5-targeting CAR-T therapy could be an attractive strategy to treat T cell malignancies. Here, we report the selection of novel CD5-targeting fully human heavy-chain variable (FHV_H) domains for the development of a biepitopic CAR, termed FHV_H3/V_H1, containing FHV_H1 and FHV_H3, which were validated to bind different epitopes of the CD5 antigen. To prevent fratricide in CD

SUBMITTER: Dai Z 

PROVIDER: S-EPMC8417515 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature