Telethon-funded Perth research to arm the body’s own cells to fight the deadliest childhood cancer

A revolutionary new treatment for an aggressive childhood cancer which kills more than half of kids who are diagnosed with it will be developed in Perth. Telethon is funding the first year of research into a ground-breaking immunotherapy that alters a patient’s own T-cells to seek out and destroy neuroblastoma tumours. Neuroblastoma is the most common solid childhood cancer, and results from immature nerve cells within the sympathetic nervous system. Around 40 children are diagnosed with it in Australia every year. It claims the lives of more children under five than any other cancer and in its most aggressive form — high-risk neuroblastoma — only one in two children survive for five years. CAR T-cell therapy has the potential to save the lives of children with high-risk neuroblastoma who do not respond to, or who have relapsed following, conventional treatment. The pioneering project is being led by Associate Professor Zlatibor Velickovic, the director of Cell and Tissues Therapies WA at Royal Perth Hospital. He said CAR (chimeric antigen receptor) T-cell therapy harnessed these specialised immune cells which have the job of patrolling the body and detecting threats like bacteria, viruses and cancer cells. “In your lifetime, you would have developed cancer cells, but nothing came out of it, because the T-cells work, and they just get rid of it. The problem arises when these T-cells sometimes don’t recognise the cancer,” Professor Velickovic said. “CAR T-cell therapy solves this problem by introducing something new to T-cells that allows them . . . to recognise the cancer and kill it.” CAR T-cell therapy involves taking T-cells from a patient and genetically engineering them to include a synthetic marker that tells them to seek out and specifically destroy cancer cells when they are returned to their body. Professor Velickovic says 90 per cent of neuroblastoma cells carried a surface antigen called GD2 ganglioside, making it a promising target for CAR T-cell therapy. With collaborators in the US, he has developed a few CAR candidates to be tested on neuroblastoma tumours in the laboratory and in animal models this year, thanks to Telethon funding. “The beauty of it is that these T-cells can go anywhere in the body because they’re in the circulatory system, so they can find it in bone marrow, in the bones and lymph nodes,” he said. “This is especially important with cancers that are metastasised and have spread around the body.” Professor Nick Gottardo, head of oncology at Perth Children’s Hospital, said the project comes after “very promising” data from a recent Italian trial of CAR T-cell therapy on children with high-risk neuroblastoma. “The trials have shown some pretty amazing responses in children with either refractory neuroblastoma which means that you couldn’t get the disease to respond properly to conventional treatment including immunotherapy, or more commonly whose disease had come back,” he said. “Importantly, for a reasonable number of those children, those responses were durable. “But the most important thing it showed that it was safe by and large. Of course there were some complications. CAR T-cells have a suicide switch, which, if the side effects are out of control, you can kill the CAR T-cells.” CAR T-cell therapy can have side effects such as immunological and neurological problems. According to Professor Velickovic, the Italian trial achieved an “incredible” 60 per cent response rate among children with refractory or relapsed neuroblastoma who currently have no effective treatment options left. “It’s essentially trying to see if our candidates could provide the same effect,” he said. “We do have a very good feeling that the CARs that we make might even be better.” Professor Gottardo said the treatment may well be a “game changer” for some children with neuroblastoma. “The first step is just to get the therapy here and deliver it to children whose disease has come back or whose disease is not responding to our standard treatments, because those children have dismal prognoses with very limited treatment options,” he said. “After that would be to incorporate it into our frontline treatments to increase the cure rates from 40 to 50 per cent to hopefully much higher than that.” The Telethon-funded research is the first time that CAR T-cell therapy is being tested on neuroblastoma in Australia. CAR T-cell therapy is currently available in WA for adult blood cancer patients who need it and it is hoped it will also be available for children later this year. Professor Velickovic said the research project will hopefully result in WA neuroblastoma patients having access to the cutting-edge treatment in Perth instead of having to travel across the country or overseas. “That’s a huge burden to the parents and to the kids,” he said. “Ultimately, the plan is to have this product, if it works, approved and readily available and affordable, as currently CAR-T cells are incredibly expensive, which significantly limits equitable access to them.” More funding is needed to progress the research beyond the preclinical stage, which is being funded by Telethon, and into clinical trials which will hopefully start in 2027 in Perth and other Australian locations. CAR T-cell therapy differs from other immunotherapies in that it is a “living therapy” and does not have to be repeatedly injected until a result is seen. “You put one cell in and it will multiply into dozens of cells, and it will keep living and killing the cancer for a number of years afterwards,” Professor Velickovic said. Henry Moon, who is five, has been receiving immunotherapy at Perth Children’s Hospital after being diagnosed with high-risk neuroblastoma in January 2024 at the age of three. His mother Danielle said Henry had been unwell for a few weeks before he was finally admitted to hospital and, after 10 days, a tumour was found above his adrenal gland. “The tumour had spread all through his bones and in his bone marrow, so unfortunately he was in the high risk category,” she said. Henry has had six rounds of chemotherapy, two operations to remove the tumour, radiotherapy and stem cell therapy. Sadly the chemotherapy has caused hearing loss and Henry now has to wear hearing aids. “The treatment has been the hardest thing we’ve ever done in our entire lives. It’s absolutely heart-breaking to see him so unwell,” Mrs Moon said. Henry happily gets on with life when he’s at home and recent scans have shown no evidence of disease in his body. But the possibility of relapse is understandably on his parents’ minds. “He’s got a 50 per cent chance of it coming back in the next five years. And if it does come back, then his percentage of survival is 10 per cent so it’s not good,” Mrs Moon said. She said CAR T-cell therapy sounded like an amazing treatment option for high-risk neuroblastoma.