Improving enzymes to help fight cancer

In New Zealand, a new cancer treatment using enzymes made by directed evolution is being developed. The enzyme is targeted to cancer cells where it activates a prodrug. This multi-step process means the prodrug is only active in cancer cells and reduces side effects for patients.

Transcript

David Ackerley (Victoria University, Wellington)

What we’re trying to develop are improved bacterial enzymes that are able to activate these compounds called prodrugs. And as the name would suggest, it’s something that has potential to be very, very toxic and drug-like, but isn't, until it becomes activated by our particular enzymes.

What it means is, because its [the prodrug] not activated in its normal sort of context, you can add it to a person’s body and they're not going to suffer any side effects at all. It’s only when it becomes activated, by enzymes inside the body or enzymes that we’ve added, that it becomes toxic.

So once we have the enzyme that’s very good at activating the prodrug, we need a delivery agent which can then deliver the gene encoding that enzyme to cancer cells, but not to healthy cells and typically, we will use something like a virus, or sometimes a bacterium, to actually deliver that gene of interest to the cancer cells.

Because what we are doing is putting in an enzyme that, in itself, can't possible harm people in any way, but it can activate these prodrugs into toxins and because it’s only their cancer cells that are being targeted, it is only those cells that will turn it into the toxic form and be harmed.

The idea is, ultimately, that the patient wouldn't get any side effects from a particular prodrug, unless it’s been activated by our enzymes.