AI-designed protein binders improved CAR T cell activity against tumors compared to antibody-derived binders in a mouse model of multiple myeloma.
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The study involved generating and screening 1,758 de novo binders targeting BCMA, CD19, and CD22 using various assays and mouse models.
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Three main issues were identified: tonic signaling, inaccessible binding sites, and off-target activity, which were addressed through computational and experimental methods.
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The optimized binder B5.I0 demonstrated superior tumor growth control in mice compared to existing BCMA-targeting CAR T therapies.
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The research highlighted the potential of evidence-based design over traditional methods in developing effective CAR T cell therapies.
