Figure 3.

IVAX vaccine and oncolytic viruses combined with checkpoint blockade. (A) Combinatorial therapy may include CTLA-4 blockade with anti-CTLA-4 mAb (leading to T cell activation and subsequent ICOS upregulation) together with the IVAX vaccine [which engages ICOS to increase T-eff migration to the tumor microenvironment (TME)]. (B) Approaches beyond antibody engineering include attenuated oncolytic virus, such as T-VEC unable to replicate in healthy cells, instead preferentially invading cancer cells. The replicating virus lyses the tumor cells and is armed, for instance with GM-CSF, which when released can recruit DCs to prime T cells to identify and destroy tumor cells. Efficacy of oncolytic virus may be improved by combination with checkpoint inhibitors, such as anti-CTLA-4 treatment to boost T cell activation.