Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety

• DOI: 10.1136/jitc-2020-000710
• Publication Date: 2020-03-24T20:24:25Z
• Authors: Yan Ge; Haiyan Wang; Jinghua Ren; Weilin Liu; Lingjuan Chen; Hongqi Chen; Junjie Ye; Enyong Dai; Congrong Ma; Songguang Ju; Zong Sheng Guo; Zuqiang Liu; David L Bartlett
• Keywords: Immune checkpoint; Immunogenic cell death

Immune checkpoint blockade is arguably the most effective current cancer therapy approach; however, its efficacy limited to patients with “hot” tumors, warranting an approach transform “cold” tumors. Oncolytic viruses (especially properly armed ones) have positive effects on almost every aspect of cancer–immunity cycle and can change cancer–immune set point a tumor. Here, we tested whether oncolytic vaccinia virus delivering tethered interleukin 12 (IL-12) could turn tumor into while avoiding IL-12’s systemic toxicity. Our data demonstrated that IL-12 be maintained in without treatment-induced toxic side effects. Moreover, treatment facilitated infiltration more activated CD4 + CD8 T cells less Tregs, granulocytic myeloid-derivedsuppressor cells, exhausted increased interferon γ decreased transforming growth factor β, cyclooxygenase-2, vascular endothelial expression, leading transformed, immunogenic tumors improved survival. Combined programmed cell death 1 blockade, expressing cured all mice late-stage colon cancer, suggesting immediate translatability clinic.