Diorio C, Murray R, Naniong M, et al. Cytosine Base Editing Enables Quadruple-Edited Allogeneic CAR-T Cells for T-ALL. Blood. 2022; (doi: 10.1182/blood.2022015825).
Some variations of allogeneic chimeric antigen receptor T cell (CAR-T) therapy need multiple gene edits to achieve clinical viability, and research identifies cytosine base editing (CBE) technology as a highly promising approach for those situations. While CRISPR-Cas9 and other gene editing techniques induce DNA double-stranded breaks that can skew outcomes, CBE silences gene expression while largely avoiding unintended and unfavorable consequences. Researchers employed CBE to manufacture allogeneic 7CAR8 using four simultaneous base edits. The quadruple-edited CAR-T targeting CD7 was not associated with changes in T-cell proliferation, unwanted DNA damage response pathway activation, and/or karyotypic abnormalities following multiple edits — outcomes often observed with CRISPR-Cas9 application. In contrast, 7CAR8 cells proved to be highly effective against T-cell acute lymphoblastic leukemia (T-ALL) and have strong potential for clinical translation against relapsed and refractory T-ALL.
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