Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy is a highly effective treatment for multiple malignancies. However, one limitation is tumor antigen-heterogeneity and downregulation, which allows tumor cells to evade conventional, monospecific CAR T cells. One approach to overcome this tumor escape is by utilizing a tandem CAR recognizing two antigens. However, tandem CAR constructs often require optimization to achieve cell surface expression and function. Herein, we describe our process of designing an IL-13Rα2-B7-H3 tandem CAR. Interestingly, our original tandem CAR failed to express on the cell surface, leading to a systematic evaluation of 24 tandem constructs varying in their scFv positioning, linkers, and specific amino acids. We identified a "trouble region" in the CAR and optimized

SUBMITTER: Meehl MM 

PROVIDER: S-EPMC12360490 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature