Chimeric Antigen Cytotoxic Receptors for In-Vivo Engineering of Tumor-targeting Natural Killer Cells

Diwanji, N.; Getts, D.; Wang, Y.

doi:10.1101/2023.11.07.565144

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bioRxiv · 10.1101/2023.11.07.565144

Chimeric Antigen Cytotoxic Receptors for In-Vivo Engineering of Tumor-targeting Natural Killer Cells

Diwanji, N.·Getts, D.·Wang, Y.

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Abstract

Ex vivo chimeric antigen receptor (CAR) NK cells face challenges in manufacturing, and have limited tumor infiltration and in vivo persistency. A method leveraging mRNA-based delivery for in-vivo engineering of human NK cells could address these issues but has not been established. Here we developed an in-vivo NK cell engineering method by designing CARs that capitalize on inherent NK receptor biology for specific expression and function. These CARs utilize the Immunoreceptor Tyrosine-based Activation Motif (ITAM)-containing signaling adaptor in human NK cells for tumor destruction and cytokine response. We demonstrated that an NKp44-based CARs expression and function depend on the signaling adaptor DAP12. This approach enables precise mRNA-driven in-vivo NK cell programming against tumors, ensuring specificity and reducing off-target expression in non-immune healthy tissues.

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Diwanji, N., Getts, D., Wang, Y.. 2023-11-10. Chimeric Antigen Cytotoxic Receptors for In-Vivo Engineering of Tumor-targeting Natural Killer Cells. https://doi.org/10.1101/2023.11.07.565144

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