Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy
Open accessAbstract
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.
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Talimogene laherparepvec tested in combination with CTLA-4 or PD-1 in advanced-stage melanoma patients resulted in increased treatment response rates compared to immune checkpoint inhibitors alone.
“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).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [124]
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- Authors
- Ribas, A., Dummer, R., Puzanov, I., VanderWalde, A., Andtbacka, R. H. I., 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.
- Affiliations
- University of California, Los Angeles (US)
- University Hospital Zurich (CH)
- Roswell Park Comprehensive Cancer Center (US)
- University of Utah (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Fox Chase Cancer Center (US)
- Hospital Clínic de Barcelona (ES)
- Austin Health (AU)
- UPMC Hillman Cancer Center (US)
- University of Chicago (US)
- Amgen (United States) (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Dana-Farber Cancer Institute (US)
- The University of Sydney (AU)
- Corresponding author
- Ribas, Antoni
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 170
- Issue
- 6
- Pages
- 1109-1119.e10
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8034392
- OpenAlex
- W2750781282
- Cited by
- 1,520
- References
- 25
- Citations by year
- 2026: 114 · 2025: 100 · 2024: 143 · 2023: 163 · 2022: 182 · 2021: 231 · 2020: 218 · 2019: 181 · 2018: 170 · 2017: 15 · 2014: 1 · 2012: 1
- FWCI
- 70.39
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-08-09)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- NIH (R35 CA197633, P20CA016056)
- Australian NHMRC fellowship (APP1119059)
- Medical Foundation K8625, University of Sydney
- Amgen Inc
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- oncolytic virotherapy, talimogene laherparepvec, pembrolizumab, anti-PD-1 therapy, advanced melanoma, intratumoral T cell infiltration, CD8+ T cells, PD-L1 expression, interferon-gamma, tumor microenvironment, combination immunotherapy, immune-related adverse events
- MeSH terms
- Combined Modality Therapy, Herpesviridae, Humans, Immunotherapy, Melanoma, Oncolytic Virotherapy, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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