Oncolytic virus therapy is an attractive and rapidly developing means for treating cancer. Genetically engineered viruses, such as herpes simplex virus Type 1 (HSV-1), newcastle disease virus (NDV), reovirus and adenovirus, are designed so that virus replication is restricted to tumor cells and therefore infection causes no harm to normal tissues. In principle, infected tumor cells are destroyed by a direct oncolytic activity of the viruses. Importantly, oncolytic viruses can also function as vectors that provide amplified transgene delivery.
As the infected cancer cells are destroyed by lysis, they release new infectious virus particles to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune responses[3-4].
The first oncolytic virus to be approved by a regulatory agency was a genetically modified adenovirus named H101 by Shanghai Sunway Biotech. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer. The drug talimogene laherparepvec (OncoVex, T-VEC) was the first oncolytic virus approved for use by the FDA and EMA in 2015 for the treatment of advanced inoperable melanoma in the US and EU. In a combined decision, members of the FDA's Oncologic Drugs Advisory Committee (ODAC) and Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) voted 22-1 to recommend approval of the oncolytic immunotherapy. Originally developed under the former USSR and now registered in Latvia, the oncolytic virus RIGVIR was also registered in Georgia in February 2015.
HSV-1, has suitable features for cancer therapy: (i) HSV-1 infects most tumor cell types. (ii) A relatively low multiplicity of infection is needed for total cell killing. (iii) Antiviral drugs are available. (iv) A large genome (~152 kb) allows the insertion of large and/or multiple transgenes. (v) The host immune reactions enhance antitumor effects. (vi) Circulating anti-HSV-1 antibodies do not affect cell-to-cell spread of the virus. (vii) There are HSV-1 sensitive mouse and nonhuman primate models for preclinical evaluation. (viii) Viral DNA is not integrated into the host genome.
 Todo, T. (2012). "Active immunotherapy: oncolytic virus therapy using HSV-1." Adv Exp Med Biol 746: 178-186.
 Ferguson, M. S., et al. (2012). "Systemic delivery of oncolytic viruses: hopes and hurdles." Adv Virol 2012: 805629.
 Melcher, A., et al. (2011). "Thunder and lightning: immunotherapy and oncolytic viruses collide." Mol Ther 19(6): 1008-1016.
 Lichty, B. D., et al. (2014). "Going viral with cancer immunotherapy." Nat Rev Cancer 14(8): 559-567.
 Frew, S. E., et al. (2008). "Chinese health biotech and the billion-patient market." Nat Biotechnol 26(1): 37-53.
 Andtbacka, R. H., et al. (2015). "Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma." J Clin Oncol 33(25): 2780-2788.
 Donina, S., et al. (2015). "Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study." Melanoma Res 25(5): 421-426.
Figure from "Recent progress in the battle between oncolytic viruses and tumours." Parato, K. A., et al. (2005). Nat Rev Cancer 5(12): 965-976.