Two cancer researchers share the 2018 Nobel Prize in medicine for work on checkpoint inhibitors

Two cancer researchers, Professor James P. Allison (from the US) and Professor Tasuku Honjo (from Japan) have been awarded the 2018 Nobel prize for their discovery of using the body’s own immune system to fight off some forms of cancer.

This was made known by the prize-giving Swedish Academy on Monday, October 1st, 2018.

2018 Nobel Prize awardees: Prof Allison (left) and Prof Honjo (right).

Cancer immunotherapy has recently revolutionalised the treatment for some cancers such as skin cancer (melanoma). Their discoveries have enabled us to understand better how the immune system can be manipulated to target tumours, leading to their [tumours’] complete regression. T cells, a component of the immune system is at the heart of this revolution.

What does our T cells do?

Our T cells protect us from foreign invaders by constantly scanning our bodies for foreign objects called antigens. If they encounter an antigen, they either elicit an immune response by themselves or signal other immune cells to mount an attack against the foreign molecules.

Following the research by Prof. Allison, we now know that T cells carry on their surface a molecule called CTLA4 that works by applying brake on T cells’ response to foreign invaders. Hence, T cells are unable to unleash their full potential. This, however, is a regulatory mechanism to keep T cell responses in check, thereby preventing auto-immune responses.

This seminal discovery by Prof. Allison has been translated into clinical treatment for some cancers. Blocking CTLA4 with an inhibitor, thus relieving T cells of the brake, will boost the immune system against tumours. It’s interesting to see how basic research could be translated into clinical application to treat cancer patients.

Subsequently, Prof Honjo and his team identified another molecule that regulates the activity of T cells. He termed it ‘’Programme Cell Death 1’’ or PD-1 for short. PD-1 are receptor molecules found on T cells. Interaction with its ligand called PD-L1 sends a negative regulatory signal to the T cells, thus attenuating further immune response. This is a regulatory mechanism used by our immune system to shutdown an ongoing immune response, thereby preventing autoimmunity. Cancer cells usurp this regulatory pathway to promote their own growth by overexpressing the ligands for PD-1 called PD-L1. Consequently, cancer cells are able to evade immune surveillance, grow and invade surrounding tissues. Developing inhibitors against PD-1 and/or PD-L1 was envisaged as a therapeutic means to boost the immune system against tumours.

Drug targeting both CTLA4 and PD-1 are called checkpoint inhibitors. Thanks to the seminal work of the two Nobel laureates as pharmaceutical companies are now developing drugs that specifically targets CTLA4, PD-1 and PD-L1, respectively.

Ipilimumab was among the first drugs developed against CTLA4 and it works by blocking CTLA4 thereby relieving the brake on T cells and allow them to mount an appropriate and a more aggressive immune response on cancer cells. Nivolumab is another drug developed to target PD-1. By blocking PD-1, it allows T cells to find and kill cancer cells. Nivolumab is currently being used to treat melanoma skin cancer, Hodgkin lymphoma, non-small cell lung cancer; whereas Ipilimumab has been useful in the treatment of advanced melanoma.

Although these checkpoints inhibitors do not seem to work for everyone, it has proven more clinical relevance in the last 8 years with cases of 100% tumour clearance reported, even after some cancers had spread.

According to the BCC, Prof Charles Swanton from the Cancer Research UK was very excited about the news of the two scientists wining the award. He congratulated them saying: ‘’ “Thanks to this groundbreaking work, our own immune system’s innate power against cancer has been realised and harnessed into treatments that continue to save the lives of patients. For cancers such as advanced melanoma, lung, and kidney, these immune-boosting drugs have transformed the outlook for many patients who had run out of options’’

Both award winners will share the Nobel prize sum of 870,000 euros.

My personal thoughts:

I was very excited to learn that both scientists have been awarded the Nobel prize in medicine or physiology. Few months ago, I was reading about novel ways to use immunotherapy to treat cancer and I came across the two checkpoint proteins, PD-1 and PD-L1. It was interesting to learn that our immune system has such negative regulatory mechanism to ensure that immune responses are constantly under check and balance. It was also intriguing to discover that cancer cells use such pathway to evade immune surveillance.

Awarding the researchers who have the paved way for our understanding of this immuno-regulatory mechanism was the right thing to do as their discoveries now mean that there are drugs targeting these pathways to boost our immune cells against tumours.

As an oncology graduate student, the news reawakens my hope and confidence in cancer research and reminds me that the work we do to understand how cancer develop and how to fight them [cancer] is being appreciated by the general public.

Wisdom.

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