Oncolytic vaccinia virus engineered with immunomodulatory transgenes

Class

Oncolytic vaccinia virus engineered with immunomodulatory transgenes (KaliVir Immunotherapeutics "TGI" platform)

Pathway

Direct viral oncolysis plus transgene-driven innate/adaptive immune activation

Notes

original target text: Oncolytic vaccinia virus engineered with immunomodulatory transgenes (KaliVir Immunotherapeutics "TGI" platform)

This mechanism uses vaccinia virus, a large DNA virus historically used as a smallpox vaccine, that has been re-engineered to selectively infect and destroy cancer cells while stimulating an immune response against the tumor. Vaccinia replicates preferentially in tumor cells because many cancers have defects in antiviral defense pathways, particularly interferon signaling, that normal cells retain. Once inside a tumor cell, the virus replicates until the cell ruptures (oncolysis), releasing new viral particles, tumor antigens, and danger signals that attract immune cells. To amplify this effect, the virus is engineered to carry additional genes (transgenes) encoding immune-stimulating proteins, which are produced locally within the tumor as the virus replicates. This combines direct tumor cell killing with recruitment and activation of both innate immune cells and antigen-specific T cells, aiming to convert tumors that are poorly recognized by the immune system into ones that provoke a durable antitumor response, potentially extending beyond the injected lesion. This approach is broadly relevant to solid tumors, especially those resistant to checkpoint inhibitors alone, where the underlying problem is often a lack of immune recognition rather than absence of a target antigen.