How CAR-NK Cells Could Work Better than CAR-T Cells
James Crowley, Professor of Medicine emeritus at Brown University, posted on LinkedIn:
”The major hurdle addressed is donor cell rejection by the recipient’s immune system, which the authors determined is primarily mediated by host CD8+ T cells.
To overcome rejection, the researchers engineered a single gene construct that combines a selective shRNA to knock down rejection-related HLA Class I molecules, a Chimeric Antigen Receptor (CAR) for tumor targeting, and the expression of immune checkpoint ligands like PD-L1 or single-chain HLA-E (SCE).
This integrated approach not only enabled the CAR-NK cells to evade host-mediated rejection in mouse models but also surprisingly enhanced their anti-tumor activity and provided a favorable safety profile by reducing inflammatory cytokines.”
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