Turning insect viruses into cancer therapies

Gene therapy is a pretty promising approach for lots of different diseases, and has already overcome a huge hurdle with the approval of the very first gene therapy product, Glybera, by the European Commission in 2012.

At its core, gene therapy uses a delivery vehicle to deposit a chunk of DNA in particular cells of the body. That courier is often a virus that has evolved to penetrate cells incredibly efficiently, and its genetic payload can be designed to normalise a cell if it’s simply defective, or to kill it if it’s cancerous.

But taking a human virus and reprogramming it for good rather than evil is not a trivial task. You have to be sure that there’s no risk of inadvertent infection and nasty disease, and you need it to stick around long enough to do its job. That means it has to be able to avoid detection – and destruction – by the immune system.

Happily, German scientists discovered in 1995 that an insect virus, baculovirus (shown below), is able to enter, but not replicate in, human cells. So there is no possibility of unintended illness, and since humans aren’t typically exposed to insect viruses, they don’t come under immediate memory immune attack.

baculovirus

(c) V. Dussupt

Now, a team of researchers (disclaimer: one of them was me) have put baculovirus through its paces to determine its utility as a gene therapy vehicle for prostate cancer.

When mixed with cells isolated from tumour or normal patient prostate biopsies, baculovirus delivered its DNA payload to lots of cancerous cells but relatively few normal ones. This preference for tumour cells is a great safety feature, since normal tissues wouldn’t be badly affected by the virus if it was carrying a toxic payload.

In three-dimensional models of the human prostate gland, baculovirus was able to poke its way through several layers of cells, a really important feature that boosts the rate of tumour shrinkage in real-life treatment scenarios.

These newly uncovered aspects of baculovirus behaviour are pleasingly positive, and make this virus an intriguing new delivery vehicle for prostate cancer gene therapy.

Swift, S., Rivera, G., Dussupt, V., Leadley, R., Hudson, L., MA de Ridder, C., Kraaij, R., Burns, J., Maitland, N., & Georgopoulos, L. (2013). Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy PLoS ONE, 8 (6) DOI: 10.1371/journal.pone.0065557

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