A peptide derived from the venom of Australia’s deadly funnel-web spider has been found to kill human melanoma and shows great promise for future treatment. Australia and New Zealand have one of the highest rates of melanoma in the world with 13,000 new cases of this potentially lethal cancer each year.
Professor John Miles, Professorial Research Fellow in Molecular Immunology at AITHM has been testing venom from numerous venomous species to determine how selected peptides affect the viability of different cancers, including melanoma, breast cancer and prostate cancer. He says out thousands of different compounds tested, ‘what's special about some of these is they kill melanoma cells, but not healthy, non-cancerous cells. A lot of the venoms we looked at killed everything and that's not very useful. What is needed is specificity. And these peptides showed that.’
He jointly supervised the spider venom research study together with Prof Glenn King of the University of Queensland. The researchers analysed and tested two spider peptides: the HiGom peptide, from the venom glands of Australian funnel-web spiders and the AgGom peptide from the venom of the South American mygalomorph spider. The study showed that both the AgGom and HiGom peptides preferentially killed human melanoma over healthy non-cancerous tissue.
Professor Miles says: ‘Excitingly, mice injected with HiGom peptide could supress melanoma growth. More work is needed, but higher doses of the peptide could potentially eliminate melanoma from mice.’
Fortuitously, these peptides can be made in large amounts in the laboratory which can accelerate medical development for novel anti-melanoma drugs. Prof Miles says: ‘Anything that has an effect on a highly aggressive melanoma line is something to take note of. And what's exciting about these peptides is that they are short peptides you can make for cents per gram. They are cheap as chips.’
Over six years, he has been working on a range of venoms to determine how they affect cancer and the immune system. He explains: ‘When I came into the field, I thought venoms were simple and contained just one toxin that kills you. But to my surprise, venoms are extremely complex and can contain thousands of different peptides, small molecules and all sorts of stuff. So it's not that surprising that we find venom peptides that do different things to the body.
‘Venom is one of the most rapidly evolving compounds on earth… it's very important because the predator needs to take down prey very quickly. So venom needs to perform quickly. So it's an evolutionary arms race between predator and prey.’
In another study Professor Miles with Professor Mark Smyth from the QIMR Berghofer Medical Research Institute found that by blocking a T-cell surface receptor (termed CD96) they could enhance killing of cancers in mice. We found the same expression patterns in humans which suggests CD96 blockade therapy could work in humans for cancer and infectious disease. They found 31 different human cancers may be susceptible to this new treatment.
He describes their findings as ‘quite promising’. The paper was listed among the top 10 articles of 2019 in the journal Immunology and Cell Biology.
Professor Miles explains the immune system has T-cells which can kill cancers. ‘But the problem with the immune system is we need lots of different brakes to keep T-cells in check, otherwise they'll just liquefy our insides because they're such dangerous cells. Many of our cells, tissues and organs express “don’t kill me” receptors (termed checkpoint molecules) on their surface’ In trying to hide from T-cells and escape detection by the immune system, cancers produce high amounts of these checkpoint molecules.
In 2018 Dr James Allison and Dr Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint therapy for cancer. Professor Miles says: ‘Everyone is racing to find these different checkpoint molecules to develop more therapies for more cancers.’