Immunotherapy: New pillar in treatment

Parkway Cancer Centre’s Dr Zee Ying Kiat reviews the current role of immune checkpoint inhibitors and its future in cancer treatment. Immunotherapy has become a buzzword as a form of revolutionary cancer treatment with tremendous potential. It was part of the treatment that former US President Jimmy Carter received for metastatic melanoma which had spread to his liver and brain. Thanks in part to immunotherapy, he was able to beat his cancer.

Immunotherapy uses the innate powers of the body’s own immune system to fight cancer and actually, it dates back to the 19th century.

The principle underlying immunotherapy was discovered by chance in the 1890s by a New York orthopaedic surgeon called William Bradley Coley. He found that of the cancer patients he operated on, those who developed an infection after surgery and survived, did better than those who did not develop an infection.

He theorised that the infection had kick-started the body’s immune system, which then went on to attack the cancer as well as the infection.

Over the decades, doctors have developed a greater understanding of how the body’s immune system can be harnessed to fight cancer. Key milestones along the way include the discovery that a type of immune cell known as T lymphocytes could identify molecules associated with tumours, leading to an immune response. This was a turning point because it led to the identification of checkpoints which control or modulate T lymphocytes.

In 2011, the U.S. Food and Drug Administration approved the use of ipilimumab, the first immune checkpoint inhibitor. This would revolutionise immunotherapy because the use of ipilimumab was found to significantly improve the survival rate of patients with advanced melanoma (a serious type of skin cancer).

The science of immune checkpoint inhibitors

Immune checkpoint inhibitors are the most widely used form of immunotherapy at the moment. They work by removing the “brakes” on T lymphocytes.

The T lymphocyte’s job is to scan for cellular abnormalities and infections and fight them. How hard the T lymphocyte works is influenced by various molecules stuck to its surface. Some molecules, when stimulated, lead to an inhibition T lymphocyte function. Other molecules, when stimulated, actually activate the T lymphocyte against the tumour.

Some cancers evade the body’s natural defences by stimulating molecules that inhibit T lymphocytes, thus preventing an immune response against the cancer. Immune checkpoint inhibitors are drugs that remove the “brakes” on the T cells, and thus allow them to be unleashed against cancer cells.

Apart from ipilimumab (also known as Yervoy), other checkpoint inhibitors that have gotten FDA approval are pembrolizumab (Keytruda), nivolumab (Opdivo) and atezolizumab (Tecentriq). Each of these checkpoint inhibitors have been approved for different types of cancers. For example, ipilimumab has been approved as a first-line treatment for melanoma and for patients with high risk melanoma who have had surgery.

Pembrolizumab has been approved for melanoma, non-small cell lung cancer, a small percentage of colorectal cancers which have a high mutational load, and squamous cell cancers of the head and neck. Nivolumab has been approved for melanoma, non-small cell lung cancer, kidney cancer and Hodgkin lymphoma while atezolizumab has been approved for the treatment of bladder cancer and non-small cell lung cancer.

Thanks to its track record, immunotherapy is now seen as one of the pillars of cancer treatment, together with chemotherapy, radiation therapy, surgery and targeted therapy.

The future

Given that immunotherapy has been successful against some cancers, researchers are now racing to see if it can be used effectively against others. Hundreds of ongoing studies are looking at the use of checkpoint inhibitors in tackling other types of cancer. These studies are also investigating the use of checkpoint inhibitors in combination with chemotherapy, targeted therapy and other forms of immunotherapy.

Our understanding of immunotherapy has only recently started to accelerate and there is still a lot to discover. As we learn more about checkpoint inhibitors and as other forms of immunotherapy mature, we are likely to see this form of therapy play an even larger role in the fight against cancer.

Written by Jimmy Yap



Tags: immune checkpoint inhibitors, immunotherapy, new ways to treat cancer, squamous cell carcinoma (SCC)