OncoImmunology | |
Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation | |
Dirk Jäger1  Guy Ungerechts2  Christian Grossardt2  Christine E. Engeland2  Laura Hartmann2  Rūta Veinalde2  Christof von Kalle2  Marie-Claude Bourgeois-Daigneault3  John C. Bell3  | |
[1] National Center for Tumor Diseases Heidelberg, Department of Medical Oncology;National Center for Tumor Diseases Heidelberg, Department of Translational Oncology, German Cancer Research Center;Ottawa Hospital Research Institute, Centre for Innovative Cancer Research; | |
关键词: anti-pd-l1; cancer immunotherapy; interleukin-12; measles virus; oncolytic viruses; | |
DOI : 10.1080/2162402X.2017.1285992 | |
来源: DOAJ |
【 摘 要 】
Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective. Treatment of established tumors with MeVac FmIL-12 achieved 90% complete remissions. Profiling of the tumor immune microenvironment revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL-12 ensuring potent early natural killer and effector T cell activation as well as upregulation of the effector cytokines IFN-γ and TNF-α. CD8+ T cells were found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery and elucidate mechanisms of successful immunovirotherapy.
【 授权许可】
Unknown