Immunological effects and viral gene expression determine the efficacy of oncolytic measles vaccines encoding IL-12 or IL-15 agonists

• Verfasst von: Backhaus, Paul S. [VerfasserIn]
• Verfasst von: Poth, Tanja [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Ungerechts, Guy [VerfasserIn]
• Verfasst von: Engeland, Christine Elisabeth [VerfasserIn]
• Titel: Immunological effects and viral gene expression determine the efficacy of oncolytic measles vaccines encoding IL-12 or IL-15 agonists
• Verf.angabe: Paul S. Backhaus, Rūta Veinalde, Laura Hartmann, Jessica E. Dunder, Lara M. Jeworowski, Jessica Albert, Birgit Hoyler, Tanja Poth, Dirk Jäger, Guy Ungerechts and Christine E. Engeland
• E-Jahr: 2019
• Jahr: 3 October 2019
• Umfang: 21 S.
• Fussnoten: Gesehen am 15.01.2020
• Titel Quelle: Enthalten in: Viruses
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2019
• Band/Heft Quelle: 11(2019,10) Artikel-Nummer 914, 21 Seiten
• ISSN Quelle: 1999-4915
• DOI: doi:10.3390/v11100914
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cancer immunotherapy
• Sach-SW: interleukin-12
• Sach-SW: interleukin-15
• Sach-SW: measles virus
• Sach-SW: oncolytic virus
• K10plus-PPN: 1687407010

Abstract

Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation.