In cellular immunotherapy engineering, CAR (chimeric antigen receptor) T-cell therapy against T-cell malignancies faces the mechanistic obstacle of fratricide: because target antigens on malignant T cells are also expressed on normal T cells, engineered CAR T cells expressing a receptor against such antigens kill one another and themselves rather than sparing normal cells. This is compounded by the inability to phenotypically distinguish malignant from normal T cells during manufacturing, risking contamination and therapy-resistant malignant cells; gene editing (targeted knockout of the shared antigen, and separately of the endogenous T-cell receptor to prevent graft-versus-host disease) resolves both problems and enables use of allogeneic, non-patient-specific donor cells as a single product for multiple recipients.
In cellular immunotherapy engineering, CAR (chimeric antigen receptor) T-cell therapy against T-cell malignancies faces the mechanistic obstacle of fratricide: because target antigens on malignant T …