CAR NK Cells Target Cancer and Autoimmunity

mRNA nanoparticles reprogram NK cells in vivo, inducing tumor remissions and reducing autoimmune liver damage in mice.

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MIT researchers developed antibody-targeted lipid nanoparticles that deliver mRNA to NK cells and generate CAR NK cells in vivo in mice.
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The nanoparticles achieved delivery efficiencies of up to approximately 80% in mice, while CAR expression peaked at 24 hours and was nearly undetectable by 72 hours.
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Five doses of CD19 CAR mRNA nanoparticles produced complete remission in all five mice with B-cell lymphoma, with efficacy comparable to externally manufactured CAR NK cells.
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In mice, the platform also showed activity against T-cell leukemia and melanoma, while CD3 CAR mRNA with interleukin-15 reduced autoreactive T cells and liver damage in autoimmune hepatitis.
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Repeated nanoparticle dosing was generally well tolerated in mice, although researchers detected antibodies against the targeting fragments.

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