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How shark's blood can save lives

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Matt Smith:

Welcome to the La Trobe University podcast. I would be your host, Matt Smith and I’m here today with my guest, Associate Professor Mick Foley of the Molecular Sciences Unit. He’s the head of the Foley Lab. Let’s give him a big fake round of applause. Thank you for joining me Mick.

Mick Foley:

It’s a pleasure Matt.

Matt Smith:

You’re here to talk to talk to me about the work that you’re doing with antibodies.

Mick Foley:

Yes. So, we’ve been interested in a particular type of antibody and that’s an antibody from sharks. And they are very small antibodies and very robust. Very different to the normal antibodies that you and I have in our blood streams. And I guess it was discovered about a couple decades ago that sharks have got this unusual small molecules but for a long time, it was not know what they were.

And then along the line came camels and camels of course have got this other antibody as well. And so, it turns out that sharks and camels have both got an unusual antibody and they haven’t really been found in many other creatures that people have looked at.

Why these animals should have these types of antibodies, we don’t know. It could be because sharks and camels are actually, adapted to suit quite harsh environments even though they’re very different. The salt balance and sharks for example, is very different to us because they live in a saltwater environment. But really it may just be a quirk of nature as to why the sharks and the camels ended up having these, whereas other creatures maybe have lost them over the period of evolution.

So, for some reason these two animals species have got extra antibody in the blood stream. Now, probably it’s helpful just to remind you what antibodies do. And essentially antibodies are our primary defense against infectious agents. So, if you and I get infected with a virus or a bacteria, our antibodies will be immobilized and eventually they will stick to that invading organism and they will recruit a lot of other things in the body to basically kill, either the virus or the bacteria or the viral infected cell. So, they’re an important line of defense.

Pretty much every creature above the jawed vertebrates have got these antibodies and important in defense and there’s also a lot of evidence to see, report immune surveillance for cancer and so that cancer, a lot of cancers are really an imbalance in this immune system which constantly surveys, looks for cancer cells and kills them early on. So, very important class of molecules.

Matt Smith:

It’s not just cancer that this is effective on. You’re doing work as well with malaria or in rheumatoid arthritis amongst other things I assume?

Mick Foley:

That’s right. And so, because they’re such a fundamental aspect of our defense, antibodies, either the small shark ones or the normal ones that we have, antibodies have evolved over a million of years to basically be very useful at killing lots of different things. So, anything that would basically interfere and assault our bodies, these antibodies will be able to bite, even small chemicals that get into our blood stream. We can generate an immune response against that and get antibodies and try and take them away.

So, they’re very useful. Our antibodies will target viruses, bacteria, cancers. The flipside to that of course is that like every system that works and when it works well, it works really well but when it goes wrong, you get autoimmune disease. So, these things are supposed to protect us against viruses and various other things. When there’s something wrong with the system, you get this autoimmune disease.

The antibodies actually start to attack self molecules and molecules that shouldn’t really attack inside your body and that could lead to autoimmune disease. But interestingly and another flip, people are trying to use these antibodies to actually stop autoimmune diseases. But that requires not the normal antibody but an engineered version of that antibody.

So, the shark antibodies, we’re looking at exploiting, we’ve done a lot of work on malaria because my lab gets a lot of funding from the Bill Gates Foundation and the NIH in America and the NHMRC to look at malaria and we ask the question, “Would these antibodies, these antibodies from sharks, if we could get a hold of them, would we be able to target malaria and basically kill the malaria parasites.”

And we showed for a number of papers that we published, the small antibodies will be able to attach to a molecule on the surface of the malaria parasite, stop that parasite from invading human red blood cells and therefore you should be able to stop the disease then. Now, that may not in itself be a good therapy from malaria because malaria is a disease of the developing countries and this would be a very expensive one. But we’re using it to gather as much information as we can on what we would need to do to kill malaria and then we’ll try, do other ways to basically target malaria using vaccines and things.

Matt Smith:

We’re separated from sharks by millions of years of evolution, do you have to do a lot of work on the antibodies for them to be able to function inside of human?

Mick Foley:

Not really. The reason other company that’s actually out there and we’ve got a small company called AdAlta which came from a cooperative research centre and really it was work between us at La Trobe University and Stuart Nuttall's group at the CSIRO and we basically did a lot of proof of principle studies on sharks.

Now, we haven’t actually put them into humans but there’s another company, they’re in clinical trials in humans to basically show that these antibodies can work in humans. The one thing that we need to overcome is the fact that they are small, which is useful in some ways but they not means they may get cleared from the blood very quickly.

So, there is a bit of work to be done but there’s a lot of work to be done even with human antibodies that we’ve engineered to use and there’s a classic example called herceptin, which is an antibody, a humanized antibody which is being used at the moment and it’s being given to patients to cure certain forms of breast cancer.

So, those antibodies work. They work very well. What we’re looking for is the next generation that would be cheaper, faster, easier to make and we probably have some other advantages as well.

Matt Smith:

Have you done any testing yet?

Mick Foley:

We’ve only done testing in the laboratory and as we’ve shown, that for example a shark antibody that were selected to bind to a molecule which is present on some breast cancer cell, that when we make that in the laboratory, put it into those breast cancer cell growing in tissue culture dish that that shark antibody will stop those breast cancer cells from growing.

So, it’s a good start. Has a long way to go but I think without that start, you really you can’t go any further. We need to try and make that better. We need to produce in large volumes and then we need to do some animal studies followed by patient studies.

And like everything else, all these clinical trials take a long time and an awful lot of money. So, the company at the moment is really trying to get funding to progress that forward.

Matt Smith:

This story is, and the ways that you’ve used the shark antibody has clearly ignited around the world a bit, being reported far and wide. What’s the weirdest way you’ve heard it reported?

Mick Foley:

The CEO of AdAlta, Samantha Cobb, and myself went to big bio meeting in America where all the biotechnology companies and pharmaceutical companies come together every year.

There was 20,000 people at that meeting and it was in San Diego and the Premier of Victoria John Brumby, he presented some of our data at that meeting and there was a lot of reporters there and report from the Age picked it up and a few other reporters. When I went back to my hotel room that night and check on the Web, it was reported in pretty much every newspaper in India for example.

And I was getting emails from websites for diving companies. So, scuba diving were basically, they pick up on the fact that I think we used the phrase, that it’s nice to think that shark which normally have got a bad reputation as killers of humans, sharks might be able to provide something to humans to protect them eventually. And so, it made a lot of the websites for scuba diving saying that sharks are not always bad.

I do encourage people that you still should think twice before you get into, to swim with them and in fact in our work, we really don’t go back to the sharks because we went to them about 10 years ago. We got the things that we needed from them that went away swimming in the tank and we used what we got from them to clone them into these vectors that we call them. And so basically they’re sitting in our freezer at the moment. Every time, we need a new shark antibody, we walked down the corridor to the freezer. We don’t have to go to the aquarium.

Matt Smith:

You have met the sharks that you’re working with essentially?

Mick Foley:

Well, at Stuart Nuttall basically, was the guy who originally got the blood and they were from the Melbourne Aquarium and they were small wobbegong sharks at the time that was present in the Melbourne Aquarium. So, nice creatures and very lovable but it’s nice to have a bit of glass between you and them, I think.

Matt Smith:

So, what are you looking forward to in the future? What’s next step of research?

Mick Foley:

So, we use shark antibodies a lot in our laboratories for basic research purposes. We use them study all sorts of things about malaria and other receptors but I guess from the point of view of commercializing this, we believe that is a great technology. It’s got a lot of potential but like everything else in biotechnology, it needs a lot of resources to basically get it to where it needs to be.

So, over the next year, we would like to progress the shark antibody and identify some shark antibody to a class of molecule that’s really important. They’re called GPCRs, but it’s not really important I guess. But these molecules are very important pharmaceutically.

There are a lot of current drugs are against these molecules. But there’s a lot of molecules that we don’t have drugs to and so we think the shark antibodies being so small would be able to get into the grooves in these molecules that normal, traditional antibodies can’t reach.

So, our primary aim is to showcase these shark antibodies, ensure that they’re actually better than normal antibodies that are doing certain things. And so, for that, we need to progress. Jo Casey who’s a senior scientist in the lab and Kathy Parisi who’s also a senior scientist in AdAlta in the lab are basically working very hard to get these to commercial reality.

Matt Smith:

Professor Mick Foley, thank you for your time today.

Mick Foley:

No problem, thanks Matt.