5 hours ago
14
Clinical trials of immunotherapies have rocketed in the past decade as researchers have turned their understanding of the body’s defences into powerful new treatments. Leading the pack are cancer therapies, but researchers have other conditions in their sights, from infections and allergies to brain diseases and autoimmune disorders. Here, we explore how these therapies work.
What is immunotherapy?
Immunotherapies are biological treatments that harness the immune system to prevent, control and fight diseases and other conditions. The most familiar are vaccines, which train the immune system to recognise targets such as invading pathogens. Other immunotherapies boost immune responses when they are too weak, or dampen them down when they are out of control. Still others draw on engineered immune cells or lab-made antibodies to disrupt disease processes.
When were they invented?
Efforts to prevent disease by boosting the immune system date back thousands of years, but advanced therapies for a wide range of illnesses have come to the fore in the past two decades. A global registry of clinical trials listed 1,257 trials of immunotherapies between 2006 and 2016. The figure leapt to 4,591 in the past decade. “It’s really exciting. People are starting to realise just how important the immune system is,” says Adrian Liston, an immunologist and professor of pathology at the University of Cambridge. “This is the era of immunology.”
How do cancer immunotherapies work?
Cancer patients have seen great benefits from immunotherapies and dozens are now approved for more than 30 types of cancer. Some tumours evade the body’s defences by switching off immune cells, but antibody-based drugs – called checkpoint inhibitors – reactivate them so they can recognise and attack the malignancies. Highly mutated or “hot” cancers such as melanoma can respond particularly well, but not in all patients.
Why some patients do well and others barely respond is a significant puzzle researchers hope to answer with a four-year study that launched last week. The project will recruit thousands of patients with breast, bladder, kidney and skin cancer to learn what factors affect their outcomes.
Other antibody-based medicines tackle cancer differently. A drug called herceptin binds to breast and stomach tumours and flags them for destruction, while blocking chemical signals that tell the cancer to grow. Another area of immense promise is cancer vaccines, many based on the mRNA technology used in Covid shots. More than 100 cancer vaccines, which stimulate the immune system to attack tumours, are now in trials.
Other therapies exploit immune cells themselves. In 2018, doctors treated a woman with metastatic breast cancer by harvesting immune cells that had infiltrated her tumours. They grew billions of the cells in the lab and reinfused the most potent ones back into her bloodstream. Another approach called Car-T-cell therapy engineers patients’ immune cells to hunt down cancer cells. Last month, the Jurassic Park actor Sam Neill announced he was cancer free after having the therapy for stage 3 blood cancer as part of a trial.
Samra Turajlić, the director of the Cancer Research UK Manchester Institute and head of the cancer dynamics laboratory at the Francis Crick Institute in London, says there has been a conceptual shift around the disease. “We increasingly see cancer as something that’s shaped by the immune system,” she says. “In fact, the appearance of cancer is a failure of the immune system to eliminate it in the first place.”
Can they treat other conditions?
Cancer immunotherapies tend to ramp up immune attacks; immunotherapies for other conditions aim to dampen them down. The simplest treat allergies such as hay fever and peanut intolerance by exposing people to small but increasing amounts of the allergy-triggering proteins. One recent trial in China sought to alleviate egg allergy by feeding people pancakes.
Researchers are now testing whether existing immunotherapies can help a broader range of patients. This week, a Bristol team described giving tocilizumab, an immunotherapy for rheumatoid arthritis, to people with depression. The study was too small to tell if it worked, but the researchers were encouraged by hints of improvement in depression severity, fatigue, anxiety and quality of life.
Some of the most exciting new immunotherapies draw on last year’s Nobel prizewinning work on regulatory T-cells, or Tregs. Humans have dozens of different immune cells that attack invading pathogens, but Tregs are unusual: they stand the immune system down once the threat has been dealt with.
Liston, the cofounder of a Cambridge spin-out called Aila Biotech, is developing a Treg therapy for multiple sclerosis, a disease caused by immune cells attacking the nervous system by mistake. The therapy aims to boost Tregs in the brain to call the attack off. The same approach could reduce swelling after traumatic brain injury, he says.
The potential for Tregs is vast. Therapies are in the pipeline for dementia and autoimmune diseases from type 1 diabetes and rheumatoid arthritis to lupus and chronic inflammation. One therapy under development by Peter Eggenhuizen at Monash University uses Tregs to treat inflammatory bowel disease, a condition that affects at least 7 million people globally.
“Probably half of all deaths have a component that is immunological,” says Liston. “It is an underlying theme across ageing, autoimmune diseases, allergies, infectious diseases, inflammatory diseases like diabetes. But one of the great things about the immune system is that it is very easy to change. We can adapt it to our purposes.”
