Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy

Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. [Display omitted] [Display omitted] •Oncolytic virus plus anti-PD-1 therapy favorably changed the tumor microenvironment•A high overall response rate of 62% to the combination in metastatic melanoma•A high complete response rate of 33% to the combination in metastatic melanoma•Responses to this combination appeared independent of baseline CD8+ infiltration In combination with anti-PD-1 therapy, intratumoral injection of an oncolytic virus engineered to enhance immune recognition of cancer resulted in a high response rate in patients with advanced melanoma.