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

Details

Serval ID
serval:BIB_A0D6FE5EA58F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
Journal
Cell
Author(s)
Ribas A., Dummer R., Puzanov I., VanderWalde A., Andtbacka RHI, Michielin O., Olszanski A.J., Malvehy J., Cebon J., Fernandez E., Kirkwood J.M., Gajewski T.F., Chen L., Gorski K.S., Anderson A.A., Diede S.J., Lassman M.E., Gansert J., Hodi F.S., Long G.V.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
170
Number
6
Pages
1109-1119.e10
Language
english
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.

Keywords
Antibodies, Monoclonal, Humanized/administration & dosage, Combined Modality Therapy, Herpesviridae/genetics, Humans, Immunotherapy, Melanoma/therapy, Oncolytic Virotherapy/adverse effects, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Tumor Microenvironment, T lymphocytes, anti-PD-1, biomarkers, cytotixic, interferon gamma, melanoma, oncolytic immunotherapy, oncolytic viruses, pembrolizumab, talimogene laherparepvec, tumor, tumor microenvironment
Pubmed
Web of science
Create date
28/09/2017 8:33
Last modification date
20/08/2019 15:06
Usage data