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

Antoni Ribas, Reinhard Dummer, Igor Puzanov, Vanderwalde Ari, Robert H.I. Andtbacka, Olivier Michielin, Anthony J. Olszanski, Josep Malvehy, Jonathan Cebon, Eugenio Fernandez, John M. Kirkwood, Thomas F. Gajewski, Lisa Chen, Kevin S. Gorski, Abraham A. Anderson, Scott J. Diede, Michael E. Lassman, Jennifer Gansert, F. Stephen Hodi, Georgina V. Long

Research output: Contribution to journalArticle

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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-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. Formula presented]

Original languageEnglish (US)
Pages (from-to)1109-1119.e10
JournalCell
Volume170
Issue number6
DOIs
StatePublished - Sep 7 2017

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Oncolytic Virotherapy
T-cells
Infiltration
Immunotherapy
T-Lymphocytes
Tumors
Gene expression
Toxicity
Therapeutics
Fatigue of materials
Antibodies
Testing
Chills
Tumor Microenvironment
Proteins
Fatigue
Melanoma
Fever
Clinical Trials
pembrolizumab

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ribas, A., Dummer, R., Puzanov, I., Ari, V., Andtbacka, R. H. I., Michielin, O., ... Long, G. V. (2017). Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell, 170(6), 1109-1119.e10. https://doi.org/10.1016/j.cell.2017.08.027

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. / Ribas, Antoni; Dummer, Reinhard; Puzanov, Igor; Ari, Vanderwalde; 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.

In: Cell, Vol. 170, No. 6, 07.09.2017, p. 1109-1119.e10.

Research output: Contribution to journalArticle

Ribas, A, Dummer, R, Puzanov, I, Ari, V, 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 2017, 'Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy', Cell, vol. 170, no. 6, pp. 1109-1119.e10. https://doi.org/10.1016/j.cell.2017.08.027
Ribas, Antoni ; Dummer, Reinhard ; Puzanov, Igor ; Ari, Vanderwalde ; 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. / Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. In: Cell. 2017 ; Vol. 170, No. 6. pp. 1109-1119.e10.
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AU - Andtbacka, Robert H.I.

AU - Michielin, Olivier

AU - Olszanski, Anthony J.

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AU - Kirkwood, John M.

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AU - Hodi, F. Stephen

AU - Long, Georgina V.

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N2 - 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. Formula presented]

AB - 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. Formula presented]

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