Combining an autoactivated cGAS mutant with membrane-tethered IL-12 via mRNA lipid nanoparticles promotes systemic tumor control
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An mRNA lipid nanoparticle platform co-delivering an autoactivated cGAS mutant (cGASR241E) and membrane-tethered IL-12 (IL-12TM) induced systemic antitumor immunity in mice. cGASR241E LNPs activated host STING signaling in vivo, while IL-12TM LNPs reduced regulatory T cells and restored effector function in tumor-infiltrating T cells, suppressing distal tumors across multiple mouse models. The combination also enhanced responsiveness to PD-L1 blockade; efficacy required CD8+ T cells and IFNg signaling.
Excerpted from biorxiv.org
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- biorxiv.orgCombining an autoactivated cGAS mutant with membrane-tethered IL-12 via mRNA lipid nanoparticles promotes systemic tumor control
An mRNA lipid nanoparticle platform co-delivering an autoactivated cGAS mutant (cGASR241E) and membrane-tethered IL-12 (IL-12TM) induced systemic antitumor immunity in mice. cGASR241E LNPs activated host STING signaling in vivo, while IL-12TM LNPs reduced regulatory T cells and restored effector function in tumor-infiltrating T cells, suppressing distal tumors across multiple mouse models. The combination also enhanced responsiveness to PD-L1 blockade; efficacy required CD8+ T cells and IFNg signaling.
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