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.
Pancreatic adenocarcinoma, the most common form of pancreatic cancer, accounts for roughly 90 to 95 percent of cases. It's notoriously difficult to catch early, because symptoms often don't appear until the disease has already spread
