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Ribas A , Dummer R , Puzanov I , VanderWalde A , Andtbacka RHI , Michielin O , Olszanski AJ , Malvehy J , Cebon J , Fernandez E , Kirkwood JM , Gajewski TF , Chen L , Gorski KS , Anderson AA , Diede SJ , Lassman ME , Gansert J , Hodi FS , Long GV
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy
Cell. 2017 Sep 07;170(6) :1109-1119.e10
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Abstract
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-gamma 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-gamma signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT.
Notes
1097-4172 Ribas, Antoni Dummer, Reinhard Puzanov, Igor VanderWalde, Ari Andtbacka, Robert H I Michielin, Olivier Olszanski, Anthony J Malvehy, Josep Cebon, Jonathan Fernandez, Eugenio Kirkwood, John M Gajewski, Thomas F Chen, Lisa Gorski, Kevin S Anderson, Abraham A Diede, Scott J Lassman, Michael E Gansert, Jennifer Hodi, F Stephen Long, Georgina V Clinical Trial, Phase I Journal Article United States Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027.