In a development that promises a new approach to cancer therapy, UTS researchers have developed a chemical "warhead" — known as an immunotoxin — that effectively targets malignant cells with a new toxin found in an Australian ant.
Professor Robert Raison of the Cell and Molecular Biology Department describes the ant toxin and the vehicle for delivering it as "a guided missile".
The research — funded by a $285,000 ARC Strategic Partnerships with Industry Research and Training (SPIRT) grant over three years — is being conducted by a UTS team in collaboration with industrial partner Dr Brian Baldo of NSL Health.
The team headed by Professor Raison comprises doctoral students Mr Andre Choo from Singapore, Ms Susan Lemke and postdoctoral researcher Dr Rosanne Dunn, whose doctoral thesis supervised by Professor Raison focused on this area.
The immunotoxin, which incorporates a major component from the venom of the jumper ant Myrmecia pilosula is four times more potent than an immunotoxin derived from bee venom, which the team investigated in an earlier research project.
In the earlier research, Professor Raison's team isolated melittin, a toxic protein in bee venom. They fused the gene encoding the toxic protein with the gene encoding the binding site of an antibody molecule in order to produce a new protein with strong anti-cancer properties, especially effective against the human leukaemia known as multiple myeloma.
"This new protein had the targeting potential of the antibody molecule at one end and the toxin at the other. It's a bit like a guided missile — the antibody is the guiding system and the toxin is the warhead against certain types of cancer," Professor Raison said.
He believes the team's current research involving the highly potent toxin from the venom of the jumper ant and its efficient delivery by means of an antibody mechanism to specific cancer sites in the body represents a new approach in the development of immunotoxins for cancer chemotherapy.
"The technology we've developed should be applicable to a range of cancers as laboratories elsewhere in the world will undoubtedly have other antibodies that can recognise tumour cells and thus be adapted for this chemotherapeutic purpose," he said.
"The notion of immunotoxins has been around for a long time and initially involved linking some conventional chemotherapy drugs to whole antibodies or antibody fragments. In the past decade research has concentrated on using potent toxins such as the diphtheria toxin, a toxin from the Pseudomonas bacterium and Ricin, a toxin of plant origin, all of which need to be delivered inside the cell to achieve their toxic effect .
"While researchers succeeded in linking these toxins to antibodies, they have worked well in the laboratory but in clinical trials have demonstrated some undesirable side effects.
"We believe these undesirable side effects are a consequence of the high potency of the toxins used, so we decided on a different approach, targeting less potent toxins such as bee venom that act on the cell membrane rather than within the cell itself."
In 1996 Professor Raison's team synthesised the gene that encoded the bee venom protein, linked it to the gene encoding an antibody, and showed that this immunotoxin killed tumour cells in the test-tube.
In 1998 Dr Baldo's research team identified and patented the use of the toxic protein pilosulin from the potent venom of the jumper ant.
"There were good reasons to look at the ant venom pilosulin rather than the bee venom melittin," Professor Raison said. "It was more toxic and we and our commercial partners could obtain intellectual property coverage of our research.
"We've developed a sound immunotoxin incorporating pilosulin and, in laboratory comparisons between pilosulin and melittin, we've shown that the ant venom component is far more effective than the bee venom component when used in an immunotoxin against cancer cells."
While the aim of developing a potent and site-specific "magic bullet" with minimal side effects has motivated cancer researchers throughout the world, Australia's humble jumper ant might yet provide UTS with a winner in the international cancer research stakes. The team has just commenced its new phase of testing in animal models.