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- W2890917067 abstract "Wnt/β-catenin signaling mediates cancer immune evasion and resistance to immune checkpoint therapy, in part by blocking cytokines that trigger immune cell recruitment. Inhibition of β-catenin may be an effective strategy for increasing the low response rate to these effective medicines in numerous cancer populations. DCR-BCAT is a nanoparticle drug product containing a chemically optimized RNAi trigger targeting CTNNB1, the gene that encodes β-catenin. In syngeneic mouse tumor models, β-catenin inhibition with DCR-BCAT significantly increased T cell infiltration and potentiated the sensitivity of the tumors to checkpoint inhibition. The combination of DCR-BCAT and immunotherapy yielded significantly greater tumor growth inhibition (TGI) compared to monotherapy in B16F10 melanoma, 4T1 mammary carcinoma, Neuro2A neuroblastoma, and Renca renal adenocarcinoma. Response to the RNAi-containing combination therapy was not dependent on Wnt activation status of the tumor. Importantly, this drug combination was associated with elevated levels of biomarkers of T cell-mediated cytotoxicity. Finally, when CTLA-4 and PD-1 antibodies were combined with DCR-BCAT in MMTV-Wnt1 transgenic mice, a genetic model of spontaneous Wnt-driven tumors, complete regressions were achieved in the majority of treated subjects. These data support RNAi-mediated β-catenin inhibition as an effective strategy to increase response rates to cancer immunotherapy." @default.
- W2890917067 created "2018-09-27" @default.
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- W2890917067 date "2018-11-01" @default.
- W2890917067 modified "2023-10-14" @default.
- W2890917067 title "RNAi-Mediated β-Catenin Inhibition Promotes T Cell Infiltration and Antitumor Activity in Combination with Immune Checkpoint Blockade" @default.
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- W2890917067 doi "https://doi.org/10.1016/j.ymthe.2018.09.005" @default.
- W2890917067 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6225018" @default.
- W2890917067 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30274786" @default.
- W2890917067 hasPublicationYear "2018" @default.
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