Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists

• Main Authors: Paul S. Backhaus, Rūta Veinalde, Laura Hartmann, Jessica E. Dunder, Lara M. Jeworowski, Jessica Albert, Birgit Hoyler, Tanja Poth, Dirk Jäger, Guy Ungerechts, Christine E. Engeland
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Viruses
• Subjects: cancer immunotherapy; oncolytic virus; measles virus; interleukin-12; interleukin-15
• Online Access: https://www.mdpi.com/1999-4915/11/10/914

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.