Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function.

ABSTRACT: Therapy with CD19-directed chimeric antigen receptor (CAR) T cells has transformed the treatment of advanced B-cell malignancies. However, loss of or low antigen expression can enable tumor escape and limit the duration of responses achieved with CAR T-cell therapy. Engineering bispecific CAR T cells that target 2 tumor antigens could overcome antigen-negative escape. We found that CD79a and b, which are heterodimeric components of the B-cell receptor, were expressed on 84.3% of lymphoma cases using immunohistochemistry, and 87.3% of CD79ab-positive tumors also coexpressed CD19. We generated 3 bispecific permutations: tandem, bicistronic, and pooled products of CD79a-CD19 or CD79b-CD19 CAR T cells and showed that bispecific CAR T cells prevented the outgrowth of antigen-negative cells in a

SUBMITTER: Leung I 

PROVIDER: S-EPMC10275707 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature