Research scientists at Melbourne's La Trobe University are pioneering an unconventional new technology that uses modified shark antibodies in therapeutic interventions against disease.

The process involves taking genes from sharks and modifying them in a laboratory by adding proteins that cause random mutations essentially mimicking the way the human immune system works - to develop antibodies capable of a repertoire of defensive responses.

According to the scientists, because shark antibodies are much smaller, chemically more robust and biologically more stable than conventional antibodies, they are uniquely well suited for targeted therapy - raising the prospect of new therapies that can be taken orally instead of injected.

Besides giving sharks a better press in their new role as lifesavers, the technology offers prospects for new and better therapies against such human diseases as malaria, cancers and rheumatoid arthritis.

Developed by La Trobe molecular biologist Associate Professor Mick Foley, an international leader in malarial research, and his CSIRO colleague Dr Stewart Nuttall, the scientists have built the world's first "library" of disease-targeting antibodies based on modified shark antibodies a library of potential new therapies, in effect, in a test-tube.

The scientists are showcasing their emerging technology on the world stage this week at the Victorian State Government's Bio-2008 Innovation Corridor in San Diego, California. Victorian Premier Mr John Brumby announced the scientists' innovative new role for sharks and the potential for further developing the technology in San Diego today.

"While Victorian scientists are not the first to recognise the potential of shark antibodies as a new line of defence against disease, existing technologies require shark handlers immunising the shark and letting the shark develop the antibodies," Mr Brumby said. "This technology has been patented and bears all the hallmarks of being the next generation of antibody-based diagnostic and therapeutic treatments."

According to the scientists at AdAlta, the Melbourne-based company now developing the technology at La Trobe University, shark antibodies are highly effective in killing malarial parasites in vitro, through a unique protein-binding process that blocks molecular function.

Associate Professor Foley, AdAlta's Chief Scientific Officer, and Dr Stewart Nuttall, the company's Consultant Scientist, made this breakthrough discovery in 2004, revealing that a shark antibody has a long, finger-like loop that projects from the surface and binds into a cavity on the target protein. The antibody disrupts the normal signalling chain of command and inhibits malaria protein from invading human red blood cells.

Irreverently tagged by the scientists as "giving malaria the finger", this sub-cellular sabotage conjured images of a similar spoiling process in the development of the anti-influenza pharmaceutical Relenza.

"When we saw the pictures of the shark antibody binding to a hole in the protein, we immediately thought of a situation like the flu," Associate Professor Foley says. "It's like covering up part of a keyhole. You don't even have to cover the whole keyhole, if you cover up part of it, you can't get the key in."

The scientists have since completed many studies showing that if a shark antibody selected from the library binds to a malaria protein and is then put into a malaria parasite in culture, it kills the parasite.

Recognition of the therapeutic potential of shark antibodies however means other biotechnology companies are also working in this space, including Haptogen, a Scottish biotechnology company recently acquired by Wyeth, a major pharmaceutical company.

Unlike AdAlta, Associate Professor Foley says, Haptogen obtains shark antibodies by immunising sharks and harvesting their blood.

"We take the genes from normal sharks and put them into a genetic vector then put in random bits of protein, similar to what the human immune system does. This 'library' is in a single test tube in the freezer. We can select antibodies in the laboratory and by maturing and optimising these you will get something that binds very tightly," says Associate Professor Foley.

"The aim is to use these shark antibodies as a way of finding high-affinity binding agents to bind to anything we want such as a molecule on cancer cells, or inflammatory proteins that you could then use in therapy."

Unlike their UK-based competitors who recently advertised for "experienced biologists with shark-handling abilities", Associate Professor Foley says, AdAlta's work is strictly lab and land- based.

""Because their IP depends on immunising the shark and letting the shark develop the antibodies, they need shark handlers. We don't. We go to the fridge and select a shark antibody on our desired target. It's all done in the laboratory. It is quicker, more efficient … and a bit safer," he says.

Images available. Picture opportunities: at Bio 2008 and La Trobe University.

Contact details

Chief Scientific Officer/Associate Professor Mick Foley
La Trobe T: +61 3 9479 5159
M: +61 434 604 811
Email: m.foley@latrobe.edu.au
(At Bio 2008: Use mobile no.)

AdAlta CEO: Samantha Cobb
M: +61 407 899 867
E: s.cobb@adalta.com.au

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