Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22.

ABSTRACT: Despite high remission rates following CAR-T cell therapy in B-ALL, relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may reduce the likelihood of antigen loss, thus improving sustained remission rates. A systematic approach to the generation of CAR constructs incorporating two target-binding domains led to several novel CD19/CD22 bivalent CAR constructs. Importantly, we demonstrate the challenges associated with the construction of a bivalent CAR format that preserves bifunctionality against both CD19 and CD22. Using the most active bivalent CAR constructs, we found similar transduction efficiency compared to that of either CD19 or CD22 single CARs alone. When expressed on hu

SUBMITTER: Qin H 

PROVIDER: S-EPMC6300726 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature