MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation.

ABSTRACT: Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in delayed tumor growth and improved survival in mouse models. Tumor regression was dependent on activated CD8+ T cells and Batf3+ dendritic cells. We also observed antigen spre

SUBMITTER: Bommareddy PK 

PROVIDER: S-EPMC7593827 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature