Biological Therapy with Oncolytic Herpesvirus

Oncolytic virus therapy refers to the biological therapy of tumors, using live viruses with relative tumor selectivity. Replication-restricted virus strains have been genetically engineered, which replicate selectively within tumor cells. Examples include replication-competent mutants of herpes virus, adenovirus, vesicular stomatitis virus, reovirus, and measles virus (2, 17, 37, Martuza, 2000; 56, 63). In particular, replication-competent recombinant HSV strains may offer distinct advantages in oncolytic therapy of epithelial tumors: (a) HSV is highly infectious to tumors of epithelial origin, resulting in high efficacy (70); (b) there is considerable redundancy in HSV receptors, which makes the loss of HSV receptors by tumors due to mutations less likely; (c) antiherpetic drugs are commercially available, which may be used clinically to control undesired side effects, should local or systemic spread of the virus occur; and (d) because of its large genome, HSV offers ample packaging opportunities – up to 30 kb – without affecting viral replication in cancer cells.