Cool science inspired Nobel prize-winning treatment for cancer

Written by Abigail Beall on October 5, 2018. Posted in Current News

What if your own immune system could defeat cancer? This year’s Nobel prize for medicine, awarded to James Allison and Tasuku Honjo, shines a light on one of the most promising efforts in the fight against the disease.

The treatment, known as the immune checkpoint blockade, gives hope to patients with previously untreatable diagnoses like lung cancer and advanced melanoma. It works by targeting the immune system, prompting the body’s own immune cells to attack dangerous tumours. The Nobel committee said the project was creating “a new pillar in cancer therapy”.

Different ways to tackle cancer include surgery and radiation, and some of these kind of treatments have been awarded previous Nobel prizes. But unlike previous cancer therapies, the immune checkpoint blockade does not target the cancer cells themselves.

Instead, it targets the brakes, or the checkpoints, of the immune system. This difference is one reason why the discoveries that led to this treatment are so important, the team behind the Nobel prize award said on Monday.

The development of the immune checkpoint blockade treatment has been more than 30 years in the making. Allison and Honjo worked separately during the 1990s on fundamental research that made the development of this cancer therapy possible.

Allison, who was at the University of California, Berkeley at the time, was looking into a protein called CTLA-4. It works as a kind of brake on the immune system, by attaching to immune cells called T-cells. Then, in 1994, Allison and colleagues came up with an antibody that could fuse to the protein. This prevents it from acting as a brake, thus releasing the immune T-cells, ready for them to fight.

Around the same time, in 1992, Honjo was working at Kyoto University in Japan. He discovered another protein, called PD-1, which also acts as a brake on the immune system. The protein works by a different mechanism to CTLA-4, but was equally important in discovering a way to release immune T-cells.

Both proteins have gone on to become vital in the fight against cancer. For over 100 years, researchers have been attempting to use the immune system to beat cancer. Yet progress was limited, until the discovery of these immune inhibiting proteins.

In 2010, a clinical study found the antibody for CTLA-4 worked on people with advanced melanoma, the most dangerous form of skin cancer. In 2012, another study revealed that the protein PD-1 worked against various types of cancer, including lung cancer.

A drug called ipilimumab, or by its brand name Yervoy, is an antibody that inhibits CTLA-4.

In 2001, a woman called Sharon Belvin was one of the first people to benefit from the new drug ipilimumab. She took part of in a phase I trial, making her one of the first humans to be given it. After one injection of the drug, her tumours vanished within six months.

Ipilimumab was approved by the US Food and Drug Administration (FDA) in 2011. It then became the first example of a checkpoint inhibitor drug to be given to regular patients. This kind of treatment is now used by the NHS to treat melanoma – the most dangerous form of skin cancer.

“It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade” Allison, who is now at the University of Texas, said. “They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”

Checkpoint therapy against PD-1 has been more effective than targeting CTLA-4, however. Positive results have been reported in clinical trials looking at patients with several types of cancer including lung, renal cancer, lymphoma and melanoma. It has also led to a possible treatment for metastatic cancer, a condition that had previously been considered untreatable.

However, new clinical studies suggest there might be a better way. Using a combination, targeting both CTLA-4 and PD-1, can be even more effective in patients with melanoma. This means both the prize-winners have a part to play in the success story.

“Allison’s and Honjo’s discoveries have added a new pillar in cancer therapy” said Klas Kärre, a member of the Nobel Committee and an immunologist at the Karolinska Institute in Stockholm. “The seminal discoveries by the two laureates constitutes a paradigmatic shift and a landmark in the fight against cancer” said Kärre.

“Thanks to this ground-breaking 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” said Charles Swanton, from Cancer Research UK. “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.”

The Nobel prize money of nine million Swedish kronor will be shared equally between the two winners. On winning the award, Honjo said: