Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype
Background Vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (VSV-GP) represents a potent oncolytic virus (OV). Oncolytic virotherapy is an emerging anticancer approach that uses viruses to eliminate cancer cells by direct cell lysis an...
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BMJ Publishing Group
2025-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/8/e010675.full |
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| author | Janine Kimpel Dorothee von Laer Theresa Schwaiger Guido Wollmann Jasmin Hatami Krishna Das Leonie Wolf Andreas Aufschnaiter Tobias Nolden Liesa-Marie Schreiber Brigitte Müllauer Elke Podgorschek Bart Spiesschaert Knut Elbers Zoltán Bánki |
| author_facet | Janine Kimpel Dorothee von Laer Theresa Schwaiger Guido Wollmann Jasmin Hatami Krishna Das Leonie Wolf Andreas Aufschnaiter Tobias Nolden Liesa-Marie Schreiber Brigitte Müllauer Elke Podgorschek Bart Spiesschaert Knut Elbers Zoltán Bánki |
| author_sort | Janine Kimpel |
| collection | DOAJ |
| description | Background Vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (VSV-GP) represents a potent oncolytic virus (OV). Oncolytic virotherapy is an emerging anticancer approach that uses viruses to eliminate cancer cells by direct cell lysis and induction of an antitumor immune response. Immunomodulatory cargos expressed by OVs hold the potential to further enhance this antitumor immune response.Methods To evaluate interleukin-12 (IL-12) as an immunomodulatory cargo encoded by VSV-GP, we used a subcutaneous tumor model by mixing type I interferon (IFN) competent murine lung epithelial cells (TC-1), which are largely resistant to VSV-GP in vivo, with VSV-GP permissive IFN-α receptor knockout TC-1 cells (TC-1ifnar1−/−).Results This mixed model supports prolonged viral replication and subsequent IL-12 production. Oncolytic virotherapy with VSV-GP and VSV-GP-IL12 of parental TC-1 tumors did not lead to tumor control, whereas virus treatment in the TC-1/TC-1ifnar1−/− mixed tumors showed prolonged survival. Furthermore, VSV-GP-IL12 was even more effective than VSV-GP treatment. Analysis of CD8+ T cell responses revealed phenotypic differences of activated CD8+ T cells between VSV-GP and VSV-GP-IL-12 treatment, whereby VSV-GP-IL12-induced CD8+T cells displayed a phenotype described for long-lived effector cells (LLEC). Depletion experiments indicated that CD8+ T cells, and not NK cells, were responsible for the improved efficacy observed with VSV-GP-IL12 treatment.Conclusions Taken together, we have demonstrated that oncolytic virotherapy using VSV-GP encoding IL-12 induces CD8+ T cell responses characterized by an LLEC phenotype, a cell population that is likely a crucial component of antitumor immunity. |
| format | Article |
| id | doaj-art-762f3cc2cb344cdb86e46b375b58ded1 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-762f3cc2cb344cdb86e46b375b58ded12025-08-21T03:45:12ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2024-010675Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotypeJanine Kimpel0Dorothee von Laer1Theresa Schwaiger2Guido Wollmann3Jasmin Hatami4Krishna Das5Leonie Wolf6Andreas Aufschnaiter7Tobias Nolden8Liesa-Marie Schreiber9Brigitte Müllauer10Elke Podgorschek11Bart Spiesschaert12Knut Elbers13Zoltán Bánki141 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria1 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria3 Christian Doppler Laboratory for Viral Immunotherapy, Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria1 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria1 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria4 Department of Internal Medicine V, Tyrolean Cancer Research Center, Medical University of Innsbruck, Innsbruck, Tyrol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria3 Christian Doppler Laboratory for Viral Immunotherapy, Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria1 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria2 ViraTherapeutics GmbH, Rum, Tyrol, Austria1 Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, AustriaBackground Vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (VSV-GP) represents a potent oncolytic virus (OV). Oncolytic virotherapy is an emerging anticancer approach that uses viruses to eliminate cancer cells by direct cell lysis and induction of an antitumor immune response. Immunomodulatory cargos expressed by OVs hold the potential to further enhance this antitumor immune response.Methods To evaluate interleukin-12 (IL-12) as an immunomodulatory cargo encoded by VSV-GP, we used a subcutaneous tumor model by mixing type I interferon (IFN) competent murine lung epithelial cells (TC-1), which are largely resistant to VSV-GP in vivo, with VSV-GP permissive IFN-α receptor knockout TC-1 cells (TC-1ifnar1−/−).Results This mixed model supports prolonged viral replication and subsequent IL-12 production. Oncolytic virotherapy with VSV-GP and VSV-GP-IL12 of parental TC-1 tumors did not lead to tumor control, whereas virus treatment in the TC-1/TC-1ifnar1−/− mixed tumors showed prolonged survival. Furthermore, VSV-GP-IL12 was even more effective than VSV-GP treatment. Analysis of CD8+ T cell responses revealed phenotypic differences of activated CD8+ T cells between VSV-GP and VSV-GP-IL-12 treatment, whereby VSV-GP-IL12-induced CD8+T cells displayed a phenotype described for long-lived effector cells (LLEC). Depletion experiments indicated that CD8+ T cells, and not NK cells, were responsible for the improved efficacy observed with VSV-GP-IL12 treatment.Conclusions Taken together, we have demonstrated that oncolytic virotherapy using VSV-GP encoding IL-12 induces CD8+ T cell responses characterized by an LLEC phenotype, a cell population that is likely a crucial component of antitumor immunity.https://jitc.bmj.com/content/13/8/e010675.full |
| spellingShingle | Janine Kimpel Dorothee von Laer Theresa Schwaiger Guido Wollmann Jasmin Hatami Krishna Das Leonie Wolf Andreas Aufschnaiter Tobias Nolden Liesa-Marie Schreiber Brigitte Müllauer Elke Podgorschek Bart Spiesschaert Knut Elbers Zoltán Bánki Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype Journal for ImmunoTherapy of Cancer |
| title | Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype |
| title_full | Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype |
| title_fullStr | Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype |
| title_full_unstemmed | Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype |
| title_short | Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype |
| title_sort | interleukin 12 encoded by the oncolytic virus vsv gp enhances therapeutic antitumor efficacy by inducing cd8 t cell responses with a long lived effector cell phenotype |
| url | https://jitc.bmj.com/content/13/8/e010675.full |
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