Fighting Cancer Within

'It's Incredible, Like Science Fiction': How a New Wave of Immunotherapy is Eliminating Cancers.

After nearly 100 years of development, treatments that bolster the body's immune system to fight cancer are coming of age – and saving patients' lives.

When 71-year-old Maureen Sideris was treated for colon cancer in 2008, she had to go under the knife. Her treatment was successful, but the post-operative recovery process was gruelling.

Fourteen years later, Sideris, who lives in New York, was diagnosed with oesophageal cancer – and this time, her treatment, offered through a clinical trial, looked radically different. Every three weeks, she travelled to Memorial Sloan Kettering Cancer Center in New York City for 45 minute-long infusions of a drug called dostarlimab.

After just four months of treatment, Sideris' tumour had disappeared – without surgery, chemotherapy or radiation, and with her only major side effect being adrenal insufficiency that causes fatigue. "It's unbelievable," she says. "It's almost like science fiction."

And yet, it's real. Sideris is one of a growing number of patients to benefit from immunotherapy for cancer, a treatment method hitting its stride after more than a century of development. With it comes the promise of personalised therapy, long-term cancer remission and fewer side-effects than other treatments such as chemotherapy and radiotherapy.

"I get choked up and have goosebumps," says Jennifer Wargo, a professor of surgical oncology and an immunotherapy researcher at MD Anderson Cancer Center in Texas. "People are living, and living with good quality lives. We're talking about cures."

The body has a natural ability to "detect and eliminate cells that look like not-you," explains Karen Knudsen, chief executive of the Parker Institute for Cancer Immunotherapy, a US nonprofit that furthers immunotherapy development. If all is working well, that should include cells that have become cancerous. But sometimes, cancer cells evade or outsmart that system, leading to dangerous unchecked growth. They hide, in plain sight, indistinguishable from the healthy cells around them.

Immunotherapy's goal is to unmask those cancer cells so the immune system can see them for what they are. It bolsters the immune system's defences so it can locate and destroy cancerous cells – with potentially incredible results.

How immunotherapy fights cancer today

Two of the best-known forms of immunotherapy are CAR T-cell therapies and immune checkpoint inhibitors. CAR T-cell therapies involve extracting T cells (the highly specific immune cells that hunt down and kill off particular foreign invaders) from a patient's blood, modifying them in a lab so they can find and attack cancer cells and then letting the souped-up T cells loose in the body. These therapies are currently used to treat blood cancers. 

Immune checkpoint inhibitors, meanwhile, are drugs that disable a built-in "off" switch in the immune system. This safeguard has an important purpose – it prevents overly aggressive immune responses that damage healthy cells. Some cancer cells can flip the off switch, however, causing the T cells to stand down so they escape detection. Immune checkpoint inhibitors prevent that from happening, meaning that the T cells identify the cancer cells as a threat and launch an assault. The scientists who pioneered this innovation won a Nobel Prize in 2018, and the drugs are today used across many cancer classes.

Still, both methods have limitations. Although research is ongoing, scientists have struggled to make CAR T-cell therapies work against solid tumours (as opposed to blood cancers), which account for more than 90% of new diagnoses. The treatment is also expensive and labour-intensive to administer.

Immune checkpoint inhibitors, meanwhile, can come with a "kaleidoscope of side effects," says Samra Turajlic, a medical oncologist at the Francis Crick Institute in London. That is because the immune system's off-switches are meant to prevent the body from attacking its own tissues and removing that defence may therefore endanger non-cancerous cells as well as tumours. According to the US National Cancer Institute, common side effects include skin rashes, diarrhoea and fatigue, while in rare cases it can cause inflammation of the liver, heart and kidneys.

That trade-off may be worth it, if the drug controls an aggressive cancer. But it doesn't always work that way. A major problem facing the entire oncology field, Turajlic says, is that no immunotherapy works in 100% of recipients. There are many potential reasons, ranging from the structure of the tumour, which can reduce its accessibility to the immune system, to the characteristics of immune cells themselves.

In general, somewhere between 20% and 40% of patients respond to immunotherapy. That means a lot of patients – the majority, in fact – are opening themselves up to side effects, not to mention wasted time and hope, without much upside.

- Author: Jamie Ducharme, BBC