Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy
By Antoni Ribas, R. Dummer, I. Puzanov, A. VanderWalde, R. Andtbacka, Olivier Michielin, A. Olszanski, J. Malvehy, J. Cebon, Eugenio Fernandez and 10 more. Cell, 2017
1,415 citations recorded by the source corpus.
SUMMARY 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.
Subfields: Genetics, Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/42d9e131b23af31d58e45093425511e0543ac99a
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Oncology
Citations in the corpus
- From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) (2018, positive): “Intratumoral application of NDV in animal models has been reported to reduce therapeutic resistance to checkpoint inhibitory antibodies (92) and to mediate systemic antitumor effects.”
- Cold Tumors: A Therapeutic Challenge for Immunotherapy (2019, background): “It has been recently shown in a melanoma phase I trial that use of oncolytic viro-therapy was able to convert a cold into hot tumor, as patients with a low level of immune cell infiltrate and a negative IFNγ signature before treatment responded well to the combination of talimogene laherparepvec wit”
- Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018, background): “The virus has been tested in recent clinical trials in combination with either CTLA-4 or PD-1 in advanced-stage melanoma patients, resulting in increased treatment response rates compared to the immune checkpoint inhibitors alone (123, 124).”