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Sydney Morning Herald
15 hours ago
- Health
- Sydney Morning Herald
CD96: How Mark Smyth hoped to build a cancer-buster
CD96 is a receptor protein on the surface of two types of immune cells: natural killer cells and killer T cells. They are responsible for continuously screening our bodies for foreign invaders. Killer T cells typically reside in our lymph nodes (in the neck and armpits; they swell when we get sick) and spleen. Our lymphatic system can be seen as our body's sewer piping – if there's a foreign invader, it will show up here sooner or later. T cells have a main receptor that can sense foreign nasties, plus lots of secondary receptors. When the main receptors get a hit, they massively multiply and leave the sewers to attack the invader. 'Everything is about shape with this,' said one immunologist, speaking anonymously to discuss the Smyth matter. 'Each of your T cell receptors, you've just got this massive amount of diversity on what they look like. So you are prepared to recognise anything you might come across in your life.' The main receptor does the bulk of the work. The secondary receptors can also sense and bind to the foreign adversary; their job is to fine-tune the immune response. Now we add a key wrinkle: immune cells also need to be able to recognise normal human cells – otherwise we would be destroyed from the inside out. They do this with the secondary receptors, which look for certain proteins on our cells that mark them as friend, not foe. One last idea, before we get to CD96. Our immune system is quite effective at hunting and killing cells that become cancerous. But occasionally, a cancerous cell acquires a collection of genetic mutations that cause it to throw up a protein that mimics the ones on a healthy cell. So our immune cells leave them alone, and they grow and grow into thick tumours. A drug to melt cancer In the early 2000s, a small group of scientists, Smyth among them, argued it might be possible to use genetically engineered antibodies to gum up some of the receptors on immune cells – unleashing their destructive power on cancers. Many scientists were initially sceptical that such a technique could ever work. Smyth was an early believer, and he was right. Checkpoint inhibitors – drugs that unleash the immune system to attack cancer – are one of the great triumphs of 21st-century science. In 2018, James Allison and Tasuku Honjo were awarded the Nobel Prize for showing how the gumming up of two receptors, CTLA-4 and PD-1, revealed cancer to the immune system. Smyth dreamt CD96, his lab's focus, might one day stand alongside the work on CTLA-4 and PD-1 as powerful cancer-busting weapons. CD96 can bind to a protein called CD155. It shares this ability with two other receptors, TIGIT and CD226. Scientists first came across it in 2004 as a natural killer cell activator – it seemed to trigger natural killer cell attack. CD226 seemed to do the same thing, while TIGIT seemed to turn off the attack. To build a checkpoint inhibitor drug, you need to find and block a receptor that inhibits T cell attack – remember, we're trying to take the brakes off the immune system. An activator like CD96 is not very useful for this purpose. Then in 2014, a team including Mark Smyth published a highly influential paper in Nature Immunology. CD96 wasn't just an activator, they said. It was a competitor with CD226. Removing CD96 in mice seemed to allow more CD226 to bind – allowing the immune system to spot and attack cancer. Scientists often bury the most important lines in a paper right at the end. Here's the one from the 2014 paper co-authored by Smyth. 'Inhibition of checkpoint molecules on lymphocytes (T cells and NK cells) is proving a useful approach for the treatment of human cancers. Blocking the interaction of CD96 with CD155 may open new opportunities for increasing the recognition of tumor cells.' Smyth's team was essentially saying that it might be possible to block CD96 and create a new immune checkpoint drug. British pharma company GSK took notice. The company filed a patent in 2020 for an antibody that binds to CD96. 'The first paper indicating CD96 as a potential immuno oncology target was published by the lab of Professor Mark Smyth in 2014,' the patent reads. GSK launched a phase 1 human clinical trial of the drug, known as Nelistotug, in 2020. Results are expected later this year. Does the drug work? We don't know, as we don't have the results. The 2014 paper on CD96 has not been retracted, and GSK did a range of its own tests on CD96 that it stands behind. 'Our robust oncology research and development program, including our investigations of Nelistotug in combination with other therapies, is always based on the full breadth of scientific evidence available,' a GSK spokeswoman said. * Name has been changed to protect the source.
The Age
15 hours ago
- Health
- The Age
CD96: How Mark Smyth hoped to build a cancer-buster
CD96 is a receptor protein on the surface of two types of immune cells: natural killer cells and killer T cells. They are responsible for continuously screening our bodies for foreign invaders. Killer T cells typically reside in our lymph nodes (in the neck and armpits; they swell when we get sick) and spleen. Our lymphatic system can be seen as our body's sewer piping – if there's a foreign invader, it will show up here sooner or later. T cells have a main receptor that can sense foreign nasties, plus lots of secondary receptors. When the main receptors get a hit, they massively multiply and leave the sewers to attack the invader. 'Everything is about shape with this,' said one immunologist, speaking anonymously to discuss the Smyth matter. 'Each of your T cell receptors, you've just got this massive amount of diversity on what they look like. So you are prepared to recognise anything you might come across in your life.' The main receptor does the bulk of the work. The secondary receptors can also sense and bind to the foreign adversary; their job is to fine-tune the immune response. Now we add a key wrinkle: immune cells also need to be able to recognise normal human cells – otherwise we would be destroyed from the inside out. They do this with the secondary receptors, which look for certain proteins on our cells that mark them as friend, not foe. One last idea, before we get to CD96. Our immune system is quite effective at hunting and killing cells that become cancerous. But occasionally, a cancerous cell acquires a collection of genetic mutations that cause it to throw up a protein that mimics the ones on a healthy cell. So our immune cells leave them alone, and they grow and grow into thick tumours. A drug to melt cancer In the early 2000s, a small group of scientists, Smyth among them, argued it might be possible to use genetically engineered antibodies to gum up some of the receptors on immune cells – unleashing their destructive power on cancers. Many scientists were initially sceptical that such a technique could ever work. Smyth was an early believer, and he was right. Checkpoint inhibitors – drugs that unleash the immune system to attack cancer – are one of the great triumphs of 21st-century science. In 2018, James Allison and Tasuku Honjo were awarded the Nobel Prize for showing how the gumming up of two receptors, CTLA-4 and PD-1, revealed cancer to the immune system. Smyth dreamt CD96, his lab's focus, might one day stand alongside the work on CTLA-4 and PD-1 as powerful cancer-busting weapons. CD96 can bind to a protein called CD155. It shares this ability with two other receptors, TIGIT and CD226. Scientists first came across it in 2004 as a natural killer cell activator – it seemed to trigger natural killer cell attack. CD226 seemed to do the same thing, while TIGIT seemed to turn off the attack. To build a checkpoint inhibitor drug, you need to find and block a receptor that inhibits T cell attack – remember, we're trying to take the brakes off the immune system. An activator like CD96 is not very useful for this purpose. Then in 2014, a team including Mark Smyth published a highly influential paper in Nature Immunology. CD96 wasn't just an activator, they said. It was a competitor with CD226. Removing CD96 in mice seemed to allow more CD226 to bind – allowing the immune system to spot and attack cancer. Scientists often bury the most important lines in a paper right at the end. Here's the one from the 2014 paper co-authored by Smyth. 'Inhibition of checkpoint molecules on lymphocytes (T cells and NK cells) is proving a useful approach for the treatment of human cancers. Blocking the interaction of CD96 with CD155 may open new opportunities for increasing the recognition of tumor cells.' Smyth's team was essentially saying that it might be possible to block CD96 and create a new immune checkpoint drug. British pharma company GSK took notice. The company filed a patent in 2020 for an antibody that binds to CD96. 'The first paper indicating CD96 as a potential immuno oncology target was published by the lab of Professor Mark Smyth in 2014,' the patent reads. GSK launched a phase 1 human clinical trial of the drug, known as Nelistotug, in 2020. Results are expected later this year. Does the drug work? We don't know, as we don't have the results. The 2014 paper on CD96 has not been retracted, and GSK did a range of its own tests on CD96 that it stands behind. 'Our robust oncology research and development program, including our investigations of Nelistotug in combination with other therapies, is always based on the full breadth of scientific evidence available,' a GSK spokeswoman said. * Name has been changed to protect the source.
RNZ News
27-06-2025
- Business
- RNZ News
Prospectors flock to WA Goldfields after large nugget unearthed
A large gold nugget like this one has been found in Western Australia, about 500km north of Kalgoorlie. Photo: Dave Craw / University of Otago By Macey Turner and Katrina Tap, ABC Veteran prospector Chris MacGregor had one thought when he heard about a chunk of gold that weighed nearly a kilogram being found near a historical West Australian gold mine town recently - "you lucky people". The 895-gram nugget found by prospectors near Sandstone, 513 kilometres north of Kalgoorlie, is worth about $165,000. "I'm sure they put in the hours, which is what it's all about, and good luck to them," MacGregor said. The Perth resident is one of many visitors making the most of a booming prospecting season in the region. Amalgamated Prospectors and Leaseholders Association of WA president James Allison said the discovery of the large nugget showed "the big gold" was "still out there". "With the technology now, there's a lot of people going over old ground and still finding gold - that's why all the caravan parks - they're all full," he said. "It's just the allure. If you find an ounce of gold - that's about the size of a 10-cent piece - that's worth $5000." Gold was first found in the region by prospectors Arthur Bayley and William Ford in 1892. Australia's Golden Outback chief executive Marcus Falconer said finds such as the Sandstone nugget were "important" in keeping the mystique of the Goldfields alive. "People decide to - like back in the gold rush days - come to seek these things out," he said. City of Kalgoorlie-Boulder mayor Glenn Wilson said the current record high gold prices had certainly excited people. "There's gold fever getting around at the moment," he said. "It's great to see that people are making the most of what is a very buoyant gold price." Prospectors have been flocking to the region for 130 years but Wilson said gold tourism was a largely untapped market. "Prospectors might spend up to three or four months out on the land looking for that elusive nugget," he said. "I think there's a massive opportunity - to harness and to further understand what that prospecting community does deliver." Greg and Liz Watson own a company that operates guided prospecting camps about 60km north of Leonora. Greg and Liz Watson thought the pandemic would ruin their gold tourism business but say demand has skyrocketed since. Photo: ABC Goldfields: Macey Turner Liz Watson said the demand for their tours was insatiable this season. "We've had to expand the amount of people we have on the tours," she said. "This year I'm turning away six to 10 people a day, at least." Despite the obvious demand, the pair said running a gold tourism business involved more than just teaching people how to find the shiny stuff. "They have to be cut out for it, because you're dealing with so many people," Greg Watson said. "Anyone coming into it needs to really have a serious look at it. "You need to have full insurance. You need to be accredited in some way." Vicky Smith went on her first tour with the Watsons in 2023 and said she enjoyed the isolation and open landscape more than the idea of finding gold. So when the Watsons needed an assistant she traded in her child protection job for a six-month stint in the red dirt. "It's lovely to be out here," she said. "This is just a completely different world." Despite an almost lifelong commitment to combing through the scrub in WA's gold country, MacGregor and his detector - affectionately dubbed the "Wailing Wand" - are yet to hit the jackpot. "It's a very rare thing to come by - you've got to put in the time," he said. Chris MacGregor has been prospecting on and off for more than 40 years after picking up his first piece of gold at the age of 11. Photo: ABC Goldfields: Katrina Tap MacGregor said finding gold was only part of the joy of prospecting. He said he would keep sleeping in his swag under the stars for as long as he was able. "Don't do it for the gold - come for everything else that's out there," MacGregor said. "If you get some gold, it's a bonus." Allison said tourists hoping to strike it lucky were welcome in the region, but stressed that safety should be the number one priority. "We've seen many, many cases over the years of prospectors getting lost and perishing, and they're found within 50 metres of their vehicle," he said. Last year the bodies of a father and son were found after they went missing while prospecting in the Murchison region. The body of Vietnam veteran William Wadsworth was also found last year, months after he went missing while prospecting near Norseman. Allison said water, food, shelter and a personal locator beacon were indispensable for prospectors, who should also let people know of their plans. "It doesn't matter if you're over-prepared," he said. "You should be always looking at the 'what if'." - ABC
ABC News
27-06-2025
- Business
- ABC News
Prospectors flock to Goldfields after large nugget unearthed
Veteran prospector Chris MacGregor had one thought when he heard about a chunk of gold that weighed nearly a kilogram being found in Western Australia's Goldfields recently — "you lucky people". The 895-gram nugget found by prospectors near the Goldfields town of Sandstone is worth about $165,000. "I'm sure they put in the hours, which is what it's all about, and good luck to them," Mr MacGregor said. The Perth resident is one of many visitors making the most of a booming prospecting season in the region. Amalgamated Prospectors and Leaseholders Association of WA president James Allison said the discovery of the large nugget showed "the big gold" was "still out there". "With the technology now, there's a lot of people going over old ground and still finding gold — that's why all the caravan parks … they're all full," he said. "It's just the allure. If you find an ounce of gold – that's about the size of a 10-cent piece – that's worth $5,000." Gold was first found in the region by prospectors Arthur Bayley and William Ford in 1892. Australia's Golden Outback chief executive Marcus Falconer said finds such as the Sandstone nugget were "important" in keeping the mystique of the Goldfields alive. "People decide to – like back in the gold rush days – come to seek these things out," he said. City of Kalgoorlie-Boulder Mayor Glenn Wilson said the current record high gold prices had certainly excited people. "There's gold fever getting around at the moment," he said. Prospectors have been flocking to the region for 130 years but Cr Wilson said gold tourism was a largely untapped market. "Prospectors might spend … up to three or four months out on the land looking for that elusive nugget," he said. "I think there's a massive opportunity … to harness and to further understand what that prospecting community does deliver." Greg and Liz Watson own a company that operates guided prospecting camps about 60 kilometres north of Leonora. Ms Watson said the demand for their tours was insatiable this season. "We've had to expand the amount of people we have on the tours," she said. Despite the obvious demand, the pair said running a gold tourism business involved more than just teaching people how to find the shiny stuff. "They have to be cut out for it, because you're dealing with so many people," Mr Watson said. "Anyone coming into it needs to really have a serious look at it. "You need to have full insurance, you need to be accredited in some way." Vicky Smith went on her first tour with the Watsons in 2023 and said she enjoyed the isolation and open landscape more than the idea of finding gold. So when Greg and Liz Watson needed an assistant she traded in her child protection job for a six-month stint in the red dirt. "It's lovely to be out here," she said. Despite an almost lifelong commitment to combing through the scrub in WA's gold country, Mr MacGregor and his detector – affectionately dubbed the "Wailing Wand" – are yet to hit the jackpot. "It's a very rare thing to come by — you've got to put in the time," he said. Mr MacGregor said finding gold was only part of the joy of prospecting. He said he would keep sleeping in his swag under the stars for as long as he was able. "Don't do it for the gold — come for everything else that's out there," Mr MacGregor said. Mr Allison said tourists hoping to strike it lucky were welcome in the region, but stressed that safety should be the number one priority. "We've seen many, many cases over the years of prospectors getting lost and perishing, and they're found within 50 metres of their vehicle," he said. Last year the bodies of a father and son were found after they went missing while prospecting in the Murchison region. The body of Vietnam veteran William Wadsworth was also found last year, months after he went missing while prospecting near Norseman. Mr Allison said water, food, shelter and a personal locator beacon were indispensable for prospectors, who should also let people know of their plans. "It doesn't matter if you're overprepared," he said.
Mercury
12-06-2025
- Business
- Mercury
Mapped: Areas where Australians are striking gold
Two friends from Western Australia have struck gold, pocketing more than $160,000 after discovering large nuggets during a prospecting mission. Amalgamated Prospectors and Leaseholders Association of Western Australia President James Allison told the Kalgoorlie Miner the two men uncovered the treasure at Sandstone, a small town some 400km northwest of Kalgoorlie-Boulder. Mr Allison said the two men, who had been prospecting for decades, came across a one-ounce nugget worth more than $5000. Later that day, the pair hit the jackpot again when their detector picked up a second sound. The men dug up and unearthed another piece weighing 895 grams, worth a whopping $161,000, according to the Perth Mint spot price as of June. MORE: MCC boss' secret $2m Melb mancave revealed Aus warned: Squatters move into man's home Revealed: Block buyer torches apartments as duds Victoria is also on the cusp of a whole new gold rush, with bush blocks where owners have found the odd nugget becoming hot property. Towns across the state's former gold fields, and especially in the golden triangle bounded by Bendigo, Ballarat and Wedderburn, have wannabe prospectors hunting for cheap land to hunt for the valuable mineral. With the price of gold surging over the past decade the leading lobby group believes more and more people will be looking to stake a claim to an alluvial address. Prospectors and Mining Association of Victoria President Jason Cornish said more people had begun looking to buy a cheap bush block amid fears the state government would turn Crown land — where prospecting is currently legal — into national parks, where it is not. Stockdale & Leggo Bendigo Sales Manager Grant Hosking said he was seeing good numbers of retirees relocating from Melbourne to take up a prospecting hobby in their golden years. Buyers have been homing in on blocks anywhere from 4ha to 40ha. 'In Wedderburn, property has never sold that quick, but we are selling them very, very quickly at the moment — and getting good prices for them,' Mr Hosking said. 'And most of it is weekenders and hobby prospectors.' The Australian Government Geoscience Australia website shows a map of where gold is likely to be found and which states have greater sources of gold. It says gold is mostly found in rocks, and WA accounted for 60 per cent of Australia's gold discoveries. Primary deposits, where miners target, were in Kalgoorlie in the Super Pit, Granny Smith, St Ives, Norseman and Mount Magnet all in WA, Gympie and Ravenswood Qld, Callie NT, Stawell Vic, Cadia NSW, Henty Tas and Challenger in SA. Gold is also found in Olympic Dam, SA – the area is mined with copper and uranium. 'Mostly, gold is spread throughout the rocks and soil around us but in such low amounts that it's not worthwhile trying to get it out,' the website said. 'However, there are some places where there is enough gold to make it economic to mine.' — Additional reporting by Nathan Mawby Sign up to the Herald Sun Weekly Real Estate Update. Click here to get the latest Victorian property market news delivered direct to your inbox. MORE: Where Aus' secret religious clans really hide Sneaky bank trick stopping Aussies saving Scary reason Aus renters won't move
