Fighting cancer with vaccinia virus: teaching new tricks to an old dog.

Vaccinia virus has played a huge part in human beings' victory over smallpox. With smallpox being eradicated and large-scale vaccination stopped worldwide, vaccinia has assumed a new role in our fight against another serious threat to human health: cancer. Recent advances in molecular biology, virology, immunology, and cancer genetics have led to the design of novel cancer therapeutics based on vaccinia virus backbones. With the ability to infect efficiently a wide range of host cells, a genome that can accommodate large DNA inserts and express multiple genes, high immunogenicity, and cytoplasmic replication without the possibility of chromosomal integration, vaccinia virus has become the platform of many exploratory approaches to treat cancer. Vaccinia virus has been used as (1) a delivery vehicle for anti-cancer transgenes, (2) a vaccine carrier for tumor-associated antigens and immunoregulatory molecules in cancer immunotherapy, and (3) an oncolytic agent that selectively replicates in and lyses cancer cells.