vvDD-IL15-Ralpha

vvDD-IL15-Ralpha is an attenuated oncolytic vaccinia virus (OVV) engineered to express a superagonist fusion protein consisting of interleukin-15 (IL-15) and the IL-15 receptor alpha (IL-15Rα). The viral backbone, known as vvDD (double-deleted), features deletions in the thymidine kinase (TK) and vaccinia growth factor (VGF) genes, which restricts viral replication to rapidly dividing cancer cells with high EGFR signaling and nucleotide pools, thereby enhancing tumor selectivity and safety. Upon infection, the virus induces immunogenic cell death (oncolysis) and local secretion of the IL-15/IL-15Rα fusion protein. This superagonist complex mimics the natural trans-presentation of IL-15, providing potent and sustained stimulation of CD8+ effector memory T cells and natural killer (NK) cells within the tumor microenvironment. Developed primarily at the University of Pittsburgh, this therapy has shown significant preclinical activity in models of colon cancer and ovarian cancer, particularly when combined with PD-1/PD-L1 checkpoint blockade.

Other names

vvDD-IL15/IL15RαvvDD-IL15-Rα superagonist