Synthetic RIG-I agonist-mediated cancer immunotherapy synergizes with MAP-Kinase inhibition against BRAF mutated melanoma [YUMM1.7]
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ABSTRACT:
PROVIDER: PRJNA1119955 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29275103_1.fastq.gz | Fastqsanger.gz | |||
| SRR29275103_2.fastq.gz | Fastqsanger.gz | |||
| SRR29275104_1.fastq.gz | Fastqsanger.gz | |||
| SRR29275104_2.fastq.gz | Fastqsanger.gz | |||
| SRR29275105_1.fastq.gz | Fastqsanger.gz |
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Project description:The implementations 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 melanoma patients still remains refractory or acquires resistance to these new forms of treatment, illustrating a need for improvement. Here we report that the clinically relevant combination of MAP kinase inhibitors Dabrafenib and Trametinib synergizes 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 the individual therapies. Our study suggests that targeted activation of RIG-I with its synthetic ligand 3pRNA could vastly improve tumor control in a substantial fraction of melanoma patients receiving MAP kinase inhibitors.
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Project description:Synthetic RIG-I agonist-mediated cancer immunotherapy synergizes with MAP-Kinase inhibition against BRAF mutated melanoma
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Project description: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.
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