Jim Olsen, Fred Hutchinson Cancer Research Centre
Jim Olsen and his team from the Fred Hutchinson Cancer Research Centre in Seattle have found a way to use scorpion venom to make a ‘paint’ which shows up cancer cells. This means that surgeons can be more certain that they are taking out an entire tumour, which can limit the damage to healthy tissue.
Chris - Tell us about your technique, how does it work?
Jim - We took a peptide which comes from scorpion venom, called chlorotoxin, and we linked it to a molecule called Cy5.5 which is a little molecular beacon; it lights up. The scorpion toxin binds to cancer cells, but not to normal cells, so our idea was to inject this into the veins of a mouse that has cancer and see whether or not the chlorotoxin could carry the molecular beacon to the cancer cells and make them glow. Indeed, when we inject mice that have tumours and wait about a day or two, we can put the mice under a camera that picks up near-infrared light, the type emitted by the molecular beacon, and it’s really easy to see the tumour compared to the normal brain around it.
Kat - So you can see the tumour even inside a mouse?
Jim - The light waves that are emitted by the molecule that we made have a very short path length. This is developed mainly for surgeons who want to see whether they got all of the cancer while they were doing their operation. So the point is that the whole tumour when they open up the cavity will be glowing, and then as they take more and more of it out, the pieces that are still glowing are where the cancer is left behind.
Kat - And how sensitive is this technique? Part of the problem with cancer is it only takes a few cells to start the cancer growing again.
Jim - Well that was one of the big surprises of our study; we initially started working on this for brain cancer, and when we tested it on other models such as prostate cancer and colon cancer we found that it was sensitive for picking up these kinds of cancer as well. In one case we had an instance where it picked up a cancer as small as 2000 cells, and that’s 5000 times more sensitive than an MRI.
Kat - That’s really tiny. Tell us a bit more about this toxin, this chlorotoxin, how does it recognise cancer cells and not target healthy cells?
Jim - We believe that it’s binding to a component of the matrix metaloproteinase-2 complex, and in easy to understand terms the matrix metaloproteinase-2 complex is what cancer cells use to eat away normal tissue to make space for the cancer to grow. For that reason this complex is expressed in cancer cells but not in normal tissue.
Kat - And do you think that this paint might also be useful for spotting cancers that have spread throughout the body, or is the wavelength not strong enough to get it out of the body again?
Jim - Well, in some cases yes. For example, if a person has breast, prostate or testicular cancer and the surgeons have the cavity open, and they’re interested in seeing whether the lymph nodes are involved, the wavelength is long enough that they would be able to see whether the lymph nodes are involved. You really couldn’t do that in a scan, and be able to see things that deep in the body. We’re really talking about superficial cancers or cancers that are surgically open.
Kat - So what’s the next step for this? Are you going to start testing in patients soon?
Jim - Yeah, there are two directions that we’re going. One is to test it in patients and we’re working with a company in Cambridge, Massachusetts, to advance this as quickly as possible to human clinical trials. Because this company has already brought cholortoxin into humans there’s a lot of safety data already available and we think we could be in clinical trials within 18-24 months. The other direction we’re going with this is to see whether it could be used as a cancer screening method, so for example people who are at risk for skin cancer, would they be able to take a dose of this tracer and then go to their dermatologist and have a scan to see which moles or which areas of their skin should be biopsied. So we’re thinking about that for the more superficial cancers, like skin cancer or colon cancer.
Chris - Jim, just to finish off, are you confident that this scorpion venom based marker will bind to all kinds of cancer cells? One of the things we’ve learned about cancer is that they’re a very heterogeneous cell population, there are stem cells in there, there are mature cancer cells. Will it bind to everything, or are we going to miss some cells?
Jim - So far we’ve tested it in six different kinds of cancer, and it has lit up all of those tumours. Within an individual tumour, it looks as though in certain types of cancer it’s lighting up almost every cell, and in others there are some cells that are lighting up and some that are not. But they are so intermixed that at the level of surgery the ones that are not lighting up are entangled with the ones that are lighting up, so you can take that whole group of cells.