Virotherapy

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1 CHANGING PERCEPTIONS - VIROTHERAPY in context
2 VIROTHERAPY - a short introduction
3 LOCATING THE PRIME VIRAL 'CANDIDATE'
4 References
5 See also

[edit] CHANGING PERCEPTIONS - VIROTHERAPY in context

Surgery; Radiotherapy; Chemotherapy - the conventional triumvirate in our anti-cancer armoury. Only the latter can be harnessed once a tumour has metastasized, and even then, the prognosis is highly variable. Side-effects due to the merciless destruction of healthy cells, are often intolerable. But what if a medically approved method existed by which tumour cells could be 'precision-bombed', leaving healthy cells untouched?

The pathogenic properties of viruses have long made them Man's akaryotic nemesis. The horror unleashed by hemorrhagic fever- inducing viruses like Ebola and the Marburg virus, merely strengthen this deep-rooted perception. But supposing viruses could be bio-engineered to our benefit?

[edit] VIROTHERAPY - a short introduction

Enter VIROTHERAPY. This experimental form of cancer treatment harnesses biotechnology to convert viruses into cancer-fighting vectors.

According to Professor Amos Panet of the Hebrew University, 'viruses are reprogrammed to selectively attack cancerous cells, leaving healthy cells undamaged.'

VIROTHERAPY is not a novel idea. As early as the 1910's, doctors were noticing that cancer patients who suffered a non-related viral infection, or who had been vaccinated recently, showed signs of improvement. This has since been attributed to the production of interferon and necrosis factors in response to viral infection. These observations prompted studies to evaluate the feasibility of oncolytic viruses in animal models. 1956 saw the earliest human clinical trial with oncolytic viruses for the treatment of advanced-stage cervical cancer. Regrettably, major limitations in biotechnology suspended further research. In the intervening years, VIROTHERAPY remained elusive to the scientist; practically unknown to the lay-person.

But in 2006, researchers from the Hebrew University succeeded in isolating a variant of the Newcastle disease Virus (NDV-HUJ), an RNA virus which usually affects poultry, in order to specifically target human cancer cells. The researchers tested this new VIROTHERAPY on Glioblastoma multiforme patients, achieving promising results for the first time (see Isracast link below).

[edit] LOCATING THE PRIME VIRAL 'CANDIDATE'

Years of research lie ahead, but there is general consensus on the following:

1) A virus must have effective oncolytic properties (“onco” cancer, “lytic” destructive) to be a feasible vector in VIROTHERAPY. The virus' mode of action must be selective, propagating rapidly in cancer cells, but not in normal cells. While chemotherapy drugs only destroy ~6 cancerous cells per healthy cell destroyed, a powerful oncolytic virus should destroy > 1000 cancerous cells for every healthy cell.

2) The viral replication cycle must be sufficiently rapid to allow the virus to infect and destroy the cancer cells BEFORE the human immune system takes anti-viral action. Once the viral infection is well-established in the tumours, the immune system may assist in eliminating infected tumour tissue and/or attacking other uninfected tumour cells (now made more apparent to the immune system as a result of the virus 'drawing attention' to them by antigen presentation.)

3) Attenuated (weakened) strains of viruses must NOT be allowed to revert to their more virulent phenotype, as this could be lethal to the patient (depending on the virus in question). To prevent this from happening, if the attenuating mutation is know, the virus can be engineered to make it impossible for a reversion to occur. This was achieved with the M51 mutant of the Vesicular stomatitis virus, a single-stranded RNA virus, by deleting nucleotides where the mutation was located. This ensured the clinical safety of the virus.

4) It must be possible to manufacture large quantities of the virus. This is achieved by infecting cell cultures and harvesting the progeny viruses from the infected cells. The infected cells must produce sufficiently high titres of virus to be therapeutically viable. High-titre tolerant DNA viruses have featured prominently in recent trials, especially Herpes simplex and Adenoviridae (first isolated in tonsil tissue). But Vaccinia, from the Poxviridae family of DNA viruses, is now preferred. Vaccinia is well suited, due to its rapid and robust replication cycle, its tolerance to gene additions and deletions through biotechnology, and finally, its broad oncolytic spectrum. The latter is true because vaccinia naturally targets the EGF-Receptor pathway that is commonly mutated in a very wide range of cancers, including lung cancer, colon cancer, breast cancer and pancreatic cancer.