Immunotherapy: Harnessing the body's immune system to fight cancer

Cutting-edge immunotherapy can add high-quality years to the lives of people with advanced cancer but there can be side effects and not all tumours respond to the treatment 

Brendan Muldoon, from Sallins., Co. Kildare, has stage IV colon cancer but is living an active life thanks to immunotherapy drugs. Photograph Moya Nolan

Brendan Muldoon from Leixlip in Co Kildare has stage IV colon cancer that has spread to his liver. Yet this 49-year-old former construction worker leads a full and active life thanks to immunotherapy, a form of cancer treatment that has the potential to revolutionise cancer care.

Muldoon has just returned from a 10k walk when he sits down to chat over the phone. Walking keeps him busy now that he’s no longer able to work.

“I worked in construction until my diagnosis in 2011,” he says. “By 2018, I was so tired of not working that I convinced my boss to let me back part-time. But when Covid hit, we didn’t know if it was safe for me to work so I stopped. Walking is what I do now. I headed out the door at 9am to go for a walk on the beach. I try to do that most days as it’s great for my mental health. In the summer, I go walking at least five times a week and will do up to 20km some days.”

Muldoon’s cancer diagnosis in 2011 followed his mother’s diagnosis and death from Lynch syndrome, also known as hereditary non-polyposis colorectal cancer. “My siblings and I were advised to get tested and have a colonoscopy,” he says. “I tested positive which meant I had to have colonoscopies and CT scans every 12 months.”

That was the start of a long and arduous cycle of colonoscopies, scans, chemotherapy and surgery. “In 2014, a scan found tumours on my liver,” he says. “I had three months of chemo, surgery and a further three months of chemo. In 2017, another tumour had to be removed. In 2019, two tumours had to be removed and I had six months of chemo. Then, three months after getting the all-clear, a scan found five tumours on my liver, and I was told they were inoperable.”

In the past, this would have amounted to a death sentence, but immunotherapy has proven to be effective in treating cancers like Muldoon’s and his oncologist recommended it as the next line of treatment.

“I started immunotherapy in June 2020, and I’ve been on it ever since,” he says. “I have treatment every two weeks and my body has reacted well. I have low energy some days, but most cycles have been a walk in the park with no side effects whatsoever.”

Professor Jarushka Naidoo is a clinical medical oncologist at Beaumont Hospital in Dublin, a lung cancer clinical lead with Cancer Trials Ireland, an adjunct assistant professor of oncology at Johns Hopkins Hospital in America and an expert in immunotherapy.

Harnessing body’s defences

Immunotherapy specialist Jarushka Naidoo is the RCSI professor of medical oncology and the lung cancer clinical lead of Cancer Trials Ireland. She defines immunotherapy as “a class of medicine that harnesses the body’s own immune system to fight cancer”.

American immunologist Jim Allison was one of the pioneers in this field. In the 1980s, he and his team asked why the immune system, which typically attacks what doesn’t belong to the body, didn’t do so in the case of cancer. They discovered that cancer cells were able to trick the body into shutting down the immune system, so they looked at ways to prevent them from doing so.

Allison and his team looked at T-cells, which are the immune system’s attack troops. They found that there were proteins on these cells that could turn the immune system on and proteins, which they called checkpoints, that could turn the immune system off. Cancer cells were able to use these checkpoints to hide from the immune system. By 1994, they had developed an antibody that blocked those checkpoint proteins and enabled the body’s T-cells to go to work destroying cancerous tumours. In the process, they won the Nobel Prize in Medicine in 2018 for the part they had played in opening up a new field in cancer treatment.

Surgery had been a common treatment option for cancer since anaesthesia became available in 1846. Radiation had been used since the 1890s. Chemical warfare research during World War II led to the discovery of chemotherapy. However, these methods of cutting, burning or poisoning cancer from the body weren’t always effective and all had potentially serious side effects.

Ipilimumab became the first checkpoint inhibitor to be authorised to treat cancer when the US Food and Drug Administration approved it in 2011. “It offered treatment based on the premise that beneficial effects may come from within our own bodies, thus using our own immune system to fight against cancer,” says Naidoo. “Today, a growing number of medicines come under the umbrella of immunotherapy. Immune checkpoint inhibitor treatments are given by medical oncologists as a standard cancer treatment now for many cancers and in the US, they are approved in over 30 different cancer indications. Many of these treatments are also available in Ireland.

“Another form of immunotherapy is CAR-T cell therapy. It’s a more invasive form of chemotherapy that’s currently used to treat cancers of the blood. It’s available in St James’s Hospital Dublin.”

Immunotherapy can be administered, depending on the cancer, at different stages in an effort to defeat or halt the disease. “Every cancer is different, and treatment differs according to the type of cancer, the stage of the cancer, its genomic profile and now its immune profile. Depending on these features, immunotherapy may be either used alone or in combination with other therapies. It’s usually administered by intravenous transfusion,” says Naidoo, who is also a consultant medical oncologist at Beaumont RCSI Cancer Centre in Dublin and an adjunct assistant professor of oncology at Johns Hopkins Hospital in the US.

Helen Forristal

Killing cancer cells

Helen Forristal is the director of nursing at the Marie Keating Foundation. Over 30 years of working in oncology, she has seen how immunotherapy has developed. “I remember looking after patients with renal cancer who were on immunotherapy treatment over 20 years ago,” she says. “They were very ill and had serious side-effects. Treatment has moved on and with options such as checkpoint inhibitors, it has become much more targeted with huge benefits for patients’ overall health and wellbeing.”

This fills her with hope for the future. “We are learning all the time and we have several types of immunotherapy treatment available now,” she says. “They all work in slightly different ways, some by triggering the immune system to attack and kill cancer cells and others by attaching themselves to cancer cells, making those cells easier for the immune system to find. We should be excited about the possibilities and hope this can offer people.”

Cancer affects everyone, directly or indirectly. According to the Irish Cancer Society, one in two of us will get a cancer diagnosis in our lifetimes. “Almost 43,500 people in Ireland get cancer every year,” says the society’s head of research Dr Claire Kilty, right. “Thankfully, more people are surviving than ever before due to advances in treatment such as immunotherapy.”

However, she strikes a note of caution. “Immunotherapy offers a lot of hope for the treatment of cancer and over the last decade, it has shown significant promise in terms of patient outcome,” she says. “But while it remains a very exciting advance, there are still challenges to overcome.”

Potential side effects for one. “These are caused by the immune system becoming more active and sometimes attacking healthy body parts and causing inflammation instead of just attacking the cancer cells,” says Professor Ray McDermott, consultant medical oncologist at St Vincent’s University Hospital Dublin and clinical lead of Cancer Trials Ireland. “For example, inflammation of the skin can cause a rash, inflammation of the joints may cause pain and swelling and inflammation of the glands of the body that make hormones needed for normal function can cause problems such as fatigue, headaches and weight changes. This can happen at any time during immunotherapy treatment and even after it has finished. Therefore, patients have to be closely monitored by their oncology team.”

Naidoo has seen these side effects in patients. “In general, immunotherapy is much more tolerable than chemotherapy and only 10 to 30% of patients experience specific immune side effects from these treatments, which can usually be treated with steroid medicines or related treatments,” she says. “However, in some cases, it’s more complicated.”

Together with endocrinologist Professor Mark Sherlock, Naidoo has set up the Irish National Immunotherapy Forum (IR-TOX Team) a national group that will provide education and discussion among cancer professionals on this emerging set of set effects. This is based on a similar team effort she led and developed at Johns Hopkins University.

“We’re just at the beginning of understanding these medicines and the more of them we administer, the more we will learn,” she says. “The IR-TOX team will allow cancer professionals caring for those receiving immunotherapy across Ireland who come together to share expertise and learn from one another.”

Dr Claire Kilty - ICS

Durable results

The varied response to immunotherapy among different cancer types and even different tumours of the same cancer is another area that requires further research. “Not all cancers respond to immunotherapy, not all tumours respond the same to treatment, and relapse and resistance are big issues that need to be overcome,” says Kilty.

According to Johns Hopkins Hospital, up to 20% of cancer patients currently see durable results with immunotherapy treatment. This is a low figure, but Naidoo sees it as something to build upon. She views immunotherapy as a journey of medical discovery that could completely change how we treat cancer.

“Traditionally, someone diagnosed with advanced lung cancer had very low chances of surviving for five years but with immunotherapy, 15% of them do,” she says. “Because immunotherapy switches the immune system on, the cancer has the potential to remain quiet for years, albeit in a small number of patients. These patients will probably still have their lives cut short, but they get to live fuller and more active lives for longer. That offers a real glimmer of hope and it’s a great starting point for doctors and researchers.”

According to Cancer Trails Ireland, there were over 40 immunotherapy clinical trials involving 130 people in Ireland last year. Naidoo urges cancer patients to consider these trials as an option in their treatment. “The reason the breakthrough in immunotherapy came about was because patients enrolled in clinical trials of these medicines that ended up being successful,” she says. “Only 2% of patients in Ireland enrol in trials and we’re aiming to increase this to 6% by 2026 as per the most recent National Cancer Strategy. It’s the only way we will bring new treatments to the fore and make progress in treating cancer.”

For now, Muldoon is grateful that immunotherapy is working for him. “My tumours have stabilised since August 2021 thanks to this treatment,” he says. “It’s given me a chance to live my life.”

• World Cancer Day is tomorrow, February 4
• The Irish Cancer Society offers help and support at Freephone 1800 200 700 and at www.cancer.ie.
• The Marie Keating Foundation has resources for information and support at www.mariekeating.ie.

Immunotherapy - the facts

Immunotherapy is one of the newest ways to treat cancer, activating and enhancing the power of the body’s immune system to defeat or halt the disease.

It’s a targeted treatment in which the immune system is primed to attack cancer cells and leave healthy cells alone. In this way, it differs from chemotherapy, which simultaneously uses drugs that kill cancer cells and healthy ones.

Because it uses the body’s defence system and doesn’t affect healthy cells, the side effects of immunotherapy are generally much more tolerable than in treatments such as chemotherapy. Up to 30% of patients experience side effects, most of which can be resolved through the short-term use of steroids.

Each type of cancer is unique. Immunotherapy doesn’t work for all types and nor does it work for all people. Current statistics show that it provides durable results in 20% of cancer patients.

Checkpoint inhibitors are one of the most common forms of immunotherapy. Until their discovery, cancer was able to use so-called checkpoint proteins on T-cells to effectively turn off the body’s immune system. Checkpoint inhibitors block these proteins and enable T-cells to destroy cancer cells. Ipilimumab became the first checkpoint inhibitor to be authorised to treat cancer when the US Food and Drug Administration approved it in 2011. Checkpoint inhibitors are now being used as a treatment option for over 30 types of cancer, with many available in Ireland.

CAR-T cell therapy is a more invasive form of immunotherapy that involves re-engineering a patient’s T-cells in the lab so that they are better able to fight cancer and then re-introducing those cells to the patient’s body by transfusion. It was introduced as a treatment for lymphoma in St James Hospital in Dublin in 2021.

Trials are underway globally to understand more about immunotherapy and how it can be used to treat cancer. According to the Cancer Research Institute, 5,683 trials are looking at checkpoint inhibitors alone.