Immunotherapy explained: How it treats cancer and other diseases

Clinical trials of immunotherapies have surged over the past decade as researchers translate their understanding of the body’s immune defenses into powerful new treatments. Cancer therapies lead the field, but scientists are also targeting infections, allergies, brain diseases, and autoimmune disorders.

Immunotherapies are biological treatments that harness the immune system to prevent, control, and fight diseases. Vaccines, the most familiar form, train the immune system to recognize pathogens. Other immunotherapies boost weak immune responses or suppress overactive ones, while some use engineered immune cells or lab-made antibodies to disrupt disease processes.

Efforts to prevent disease by boosting immunity date back thousands of years, but advanced therapies have emerged in the past two decades. A global registry of clinical trials listed 1,257 immunotherapy trials between 2006 and 2016, leaping to 4,591 in the following decade. “It’s really exciting. People are starting to realise just how important the immune system is,” said Adrian Liston, an immunologist and professor of pathology at the University of Cambridge. “This is the era of immunology.”

Cancer patients have seen significant benefits, with dozens of immunotherapies now approved for more than 30 cancer types. Some tumors evade the immune system by switching off immune cells, but antibody-based drugs called checkpoint inhibitors reactivate them to recognize and attack malignancies. Highly mutated or “hot” cancers such as melanoma often respond well, though not in all patients.

Why some patients respond and others do not remains a major puzzle. A four-year study launched last week aims to answer this by recruiting thousands of patients with breast, bladder, kidney, and skin cancer to identify factors affecting outcomes.

Other antibody-based medicines target cancer differently. Herceptin binds to breast and stomach tumors, flagging them for destruction while blocking growth signals. Cancer vaccines, many using mRNA technology from COVID-19 shots, also show promise. More than 100 such vaccines, which stimulate the immune system to attack tumors, are currently in trials.

Other therapies exploit immune cells directly. In 2018, doctors treated a woman with metastatic breast cancer by harvesting immune cells that had infiltrated her tumors, growing billions in the lab, and reinfusing the most potent ones. CAR-T cell therapy engineers patients’ immune cells to hunt cancer. Last month, actor Sam Neill announced he was cancer-free after receiving this therapy for stage 3 blood cancer as part of a trial.

“We increasingly see cancer as something that’s shaped by the immune system,” said Samra Turajlić, director of the Cancer Research UK Manchester Institute and head of the cancer dynamics laboratory at the Francis Crick Institute in London. “In fact, the appearance of cancer is a failure of the immune system to eliminate it in the first place.”

Cancer immunotherapies typically ramp up immune attacks, while those for other conditions aim to dampen them. Simple allergy treatments, such as for hay fever or peanut intolerance, expose patients to small, increasing amounts of allergens. A recent trial in China sought to alleviate egg allergy by feeding people pancakes.

Researchers are testing whether existing immunotherapies can help broader patient groups. This week, a Bristol team described giving tocilizumab, an immunotherapy for rheumatoid arthritis, to people with depression. The study was too small to confirm efficacy, but hints of improvement in depression severity, fatigue, anxiety, and quality of life encouraged researchers.

Some of the most exciting new immunotherapies draw on last year’s Nobel Prize-winning work on regulatory T-cells, or Tregs. While most immune cells attack pathogens, Tregs stand the immune system down once the threat is resolved.

Liston, co-founder of Cambridge spin-out Aila Biotech, is developing a Treg therapy for multiple sclerosis, a disease where immune cells mistakenly attack the nervous system. The therapy aims to boost Tregs in the brain to halt the attack, a potential approach for reducing swelling after traumatic brain injury.

The potential for Tregs is vast. Therapies are in development for dementia, autoimmune diseases including type 1 diabetes, rheumatoid arthritis, lupus, and chronic inflammation. Peter Eggenhuizen at Monash University is using Tregs to treat inflammatory bowel disease, which affects at least 7 million people globally.

“Probably half of all deaths have a component that is immunological,” said 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.”