What is this virus – how does it work?

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It is an oncolytic virus: a virus that attacks cancer cells.

Since the 1880s, doctors have known viral infections can cause dramatic reductions in tumours.   In 1890, the Italian de Rice discovered that prostitutes with cervical cancer went into remission whenever they were vaccinated against rabies, and for several years he wandered around the Tuscan countryside kindly injecting ladies with dog saliva.

In another 20th century case, a fourteen-year old boy with lymphatic leukaemia caught chickenpox: within a few days his grotesquely enlarged liver and spleen had returned to ordinary size; his explosive white-blood cell count, shrunk nearly fifty-fold, back to normal.

But it wasn’t until the 1990s, and the boom in understanding of genetics, that scientists finally learned how to harness and enhance this effect.   Two decades later, the first results are starting to be discussed in cancer journals.

To geneticists, the science makes perfect sense. It is a fact of human biology that healthy cells are programmed to die when they become infected by a virus, because this prevents the virus spreading to other parts of the body.

But a cancerous cell is immortal; through its mutations it has somehow managed to turn off the bits of its genetic programme that enforce cell suicide.

This means that, if a suitable virus infects a cancer cell, it could continue to replicate inside it uncontrollably, and causes the cell to ‘lyse’ – or, in non-technical language, tear apart.

The progeny viruses then spread to other cancer cells nearby and repeat the process. A virus becomes, in effect, a cancer of cancer.

The Uppsala virus is a genetically engineered adenovirus. It’s scientific name is Ad5[CgA-E1A-miR122]PTD. A virus that usually causes colds in humans, it has been modified to attack neuroendocrine cancer cells.

It works in a variety of ways, in addition to the basic one described in the last paragraph.   It has also been modified to encourage the immune system to recognise and attack neuroendocrine tumours.

For more detailed information you can look at the four papers the research team at Uppsala have published, in leading peer-reviewed journals, about the development of this potential new treatment.

PAPER I

A novel chromogranin-A promoter-driven oncolytic adenovirus for midgut carcinoid therapy.

Leja J, Dzojic H, Gustafson E, Oberg K, Giandomenico V, Essand M.

Clin Cancer Res. 2007 Apr 15;13(8):2455-62.

PAPER II

Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability.

Leja J, Nilsson B, Yu D, Gustafson E, Akerström G, Oberg K, Giandomenico V, Essand M.

PAPER III

Adenovirus with hexon Tat-protein transduction domain modification exhibits increased therapeutic effect in experimental neuroblastoma and neuroendocrine tumors.

Yu D, Jin C, Leja J, Majdalani N, Nilsson B, Eriksson F, Essand M.

J Virol. 2011 Dec;85(24):13114-23. Epub 2011 Sep 28.

PAPER IV

Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells.

Leja J, Yu D, Nilsson B, Gedda L, Zieba A, Hakkarainen T, Åkerström G, Öberg K, Giandomenico V, Essand M.

Gene Ther. 2011 Nov;18(11):1052-62. doi: 10.1038/gt.2011.54. Epub 2011 Apr 14.

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