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Title: Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
Austin Authors: Ribas, Antoni;Dummer, Reinhard;Puzanov, Igor;VanderWalde, Ari;Andtbacka, Robert H I;Michielin, Olivier;Olszanski, Anthony J;Malvehy, Josep;Cebon, Jonathan S ;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
Affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA
Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
Hopitaux Universitaires de Genève, Geneva, Switzerland
University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
Centre Hospitalier Universitaire Vaudois, LaUSAnne, Switzerland
University Hospital of Zurich, Zurich, Switzerland
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
The West Clinic, Memphis, TN, USA
Dana-Farber Cancer Institute, Boston, MA, USA
Amgen Inc., ThoUSAnd Oaks, CA, USA
Merck & Co., Inc., Kenilworth, NJ, USA
Roswell Park Cancer Institute, Buffalo, NY, USA
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Amgen Inc., South San Francisco, CA, USA
The University of Chicago School of Medicine, Chicago, IL, USA
University of Pittsburgh Cancer Institute and Hillman UPMC Cancer Center, Pittsburgh, PA, USA
Fox Chase Cancer Center, Philadelphia, PA, USA
Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia
Issue Date: 7-Sep-2017
Publication information: Cell 2017; 170(6): 1109-1119.e10
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-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. VIDEO ABSTRACT.
DOI: 10.1016/j.cell.2017.08.027
ORCID: 0000-0002-3898-950X
Journal: Cell
PubMed URL: 28886381
Type: Journal Article
Subjects: T lymphocytes
interferon gamma
oncolytic immunotherapy
oncolytic viruses
talimogene laherparepvec
tumor microenvironment
Appears in Collections:Journal articles

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