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Oncolytic herpes virus
Many variants of herpes simplex virus have been considered for viral therapy of cancer; the early development of these was thoroughly reviewed in the journal ''Cancer Gene Therapy'' in 2002. This page describes (in the order of development) the most notable variants—those tested in clinical trials: G207, HSV1716, NV1020 and Talimogene laherparepvec (previously Oncovex-GMCSF).
==HSV1716==
HSV1716 is a first generation oncolytic virus developed by The Institute of Virology, Glasgow, UK, and subsequently by Virttu Biologics (formerly Crusade Laboratories, a spin-out from The Institute of Virology), to selectively destroy cancer cells. The virus has the trade name SEPREHVIR. It is based on the herpes simplex virus (HSV-1). The HSV1716 strain has a deletion of the gene ICP34.5. ICP34.5 is a neurovirulence gene (enabling the virus to replicate in neurons of the brain and spinal cord). Deletion of this gene provides the property of tumor-selective replication to the virus (i.e. largely prevents replication in normal cells, while still allowing replication in tumor cells), although it also reduces replication in tumor cells as compared to wild type HSV.
A vital part of the normal mechanism of HSV-1, the ICP34.5 protein has been proposed to condition post-mitotic cells for viral replication. With no ICP34.5 gene, the HSV-1716 variant is unable to overcome normal defences of healthy differentiated cells (mediated by PKR) to replicate efficiently. However, tumour cells have much weaker PKR-linked defences, which may be the reason why HSV1716 effectively kills a wide range of tumour cell lines in tissue culture.
An HSV1716 variant, HSV1716NTR is an oncolytic virus generated by inserting the enzyme NTR into the virus HSV1716 as a GDEPT strategy. In-vivo, administration of the prodrug CB1954 to athymic mice bearing either A431 or A2780 tumour xenografts, 48 hours after intra-tumoral injection of HSV1790, resulted in a marked reduction in tumour volumes and significantly improved survival compared to administration of virus alone. A similar approach has been taken with a variants of HSV1716 that expresses the noradrenaline transporter to deliver radioactive iodine into individual infected cancer cells, by tagging a protein that cancer cells transport. The nor-adrenaline transporter specifically transports a compound containing radioactive iodine across the cell membrane, using genes from the virus. The only cells in the body that receive a significant radiation dose are those infected and their immediate neighbours.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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