Improved antitumor activity of immunotherapy combined with BRAF and MEK inhibitors in BRAFV600E mutant melanoma

ABSTRACT: The first clinical trial testing the combination of targeted therapy with a BRAF inhibitor vemurafenib and immunotherapy with a CTLA-4 antibody ipilimumab was terminated early due to significant liver toxicities, possibly due to paradoxical activation of the MAPK pathway by BRAF inhibitors in tumors with wild type BRAF. MEK inhibitors can potentiate the MAPK inhibition in tumor, while potentially alleviating the unwanted paradoxical MAPK activation. With a mouse model of syngeneic BRAFV600E driven melanoma (SM1), we tested whether the addition of the MEK inhibitor trametinib would enhance the immunosensitization effects of the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression. Bioluminescent imaging

ORGANISM(S): Mus musculus

SUBMITTER: Jennifer Tsoi 

PROVIDER: E-GEOD-64102 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress