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Prime Editing Creates Drug-Controllable T Cell Therapies
Engineered T cells resisted tacrolimus but remained sensitive to cyclosporin, providing a potential way to select or suppress them after administration
A preclinical prime-editing platform engineered therapeutic T cells to resist tacrolimus while remaining sensitive to cyclosporin.
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In T cells from 3 patients with HAVCR2-associated lymphoma, prime editing corrected the pathogenic variant in 18.7% to 35.8% of cells and restored TIM-3 expression in up to 44.4%.
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In humanized mice, tacrolimus selection increased corrected HAVCR2 sequences to an average of 76.8% of spleen reads after 8 weeks, compared with 9.3% without selection.
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Tacrolimus-exposed, edited CD19-directed CAR T cells retained viability, proliferation, and tumor-killing activity, and maintained tumor control in mice with CD19-positive tumors.
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The researchers also tested edits for resistance to methotrexate and mycophenolate, with resistance varying by edit.
