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Synthetic RIG-I agonist-mediated cancer immunotherapy synergizes with MAP kinase inhibition against BRAF-mutated melanoma.
- Source :
-
Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2024 Jul 19; Vol. 35 (3), pp. 102283. Date of Electronic Publication: 2024 Jul 19 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- The implementation of targeted molecular therapies and immunotherapy in melanoma vastly improved the therapeutic outcome in patients with limited efficacy of surgical intervention. Nevertheless, a large fraction of patients with melanoma still remain refractory or acquire resistance to these new forms of treatment, illustrating a need for improvement. Here, we report that the clinically relevant combination of mitogen-activated protein (MAP) kinase pathway inhibitors dabrafenib and trametinib synergize with RIG-I agonist-induced immunotherapy to kill BRAF-mutated human and mouse melanoma cells. Kinase inhibition did not compromise the agonist-induced innate immune response of the RIG-I pathway in host immune cells. In a melanoma transplantation mouse model, the triple therapy outperformed individual therapies. Our study suggests that agonist-induced activation of RIG-I with its synthetic ligand 3pRNA could vastly improve tumor control in a substantial fraction of patients with melanoma receiving MAP kinase inhibitors.<br />Competing Interests: G.H. is an inventor on a patent covering synthetic RIG-I ligands. M.R. and G.H. were co-founders of Rigontec GmbH. J.L.S.-B. is a co-founder and shareholder of LAMPseq Diagnostics.<br /> (© 2024 The Authors.)
Details
- Language :
- English
- ISSN :
- 2162-2531
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Nucleic acids
- Publication Type :
- Academic Journal
- Accession number :
- 39165562
- Full Text :
- https://doi.org/10.1016/j.omtn.2024.102283