The Nobel prize for elegant idea: immunotherapy against cancer

Today in Stockholm was named the first winners of the Nobel prize in 2018. Laureates in physiology and medicine began Japanese, Tasuku Honjo and American James Ellison “for the discovery of cancer therapy, inhibition of negative immune regulation,” reads the statement on the website of the Nobel Committee.

Tasuku Honjo and James Ellison

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The laureates worked independently of each Honjo at Kyoto University, and Allison at the University of California at Berkeley. Allison studied a protein that acts as a “brake” of the immune system. He suggested the possibility of controllably release the brake so that the immune cells attacked the tumor cells. Honjo discovered another protein in the immune cells and by studying its functions, have shown that it also acts as a brake, but with a completely different mechanism.

These ideas formed the basis for a fundamentally new approach to the treatment of cancer patients. In fact, the winners for the first time in history, suggested a struggle with cancer, which is based on the external effects of radio – or chemotherapy, and mobilizing the inner resources of our body – the immune system.

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To understand the mechanism of this therapy, you need to go back a few steps back and remember how all our body can cause cancer cells. Infectious diseases are caused by external agents – bacteria and viruses. Bacteria are cells by themselves, viruses are smaller education – but they are alien. This allows the immune system in most cases to recognize and destroy them. Cancer cells are cells found in the body of a human, but mutated.

Mutations occur in our cells when dividing constantly, and our body has a whole range of mechanisms for getting rid of “sick” cells from a controlled cell death when the cell is “diagnose” disorders and self-destructs, to the same immune system. In fact, an atypical cell becomes cancerous when it acquires the ability to circumvent the protective barriers built by the body to self-improvement. In particular, cancer cells are able to “masked” from the immune system.

Therefore, traditionally there are three ways of dealing with them – a surgical removal, destruction with a type of radiation and drug effects. The Nobel prize was awarded for the implementation of the elegant idea of the cancer cells as such, and arms them against our own immune system.

Who are they?

One of the laureates of the Japanese from Kyoto, the second American from Texas. That’s what tells them a member of the prize Committee for physiology or medicine, immunologist, Professor Klas Sherra.

“Professor Allison is a scientist-immunologist, he is not a doctor. He was educated in biology, which interested him since childhood. To work on cancer therapy, he did a lot of interesting fundamental discoveries in the field of regulation of immunity. He didn’t open the “molecule-brake”, but he realized its potential for therapy,” said Sherra in an interview published on the website of the award.

“Professor Honjo – continues Sherra, doctor, he’s got a degree of doctor of medicine. But he also owns important discoveries in fundamental immunology, and he also initially did not work in cancer immunology. When he opened his mechanism of inhibition of immunity, it was the fundamental work, but later he was able to realize its practical value.”

The Secretary of the Committee, Professor Thomas Scherer, spoke about the reaction of the winners for the award.

“I have not yet managed to speak by phone with Professor Ellison, but I got through to Professor Honjo. I don’t know if he was expecting a prize, but he seemed rather surprised. And, of course, he was very pleased to receive the award, and he also stressed that he was happy to share it with Dr. Allison,” said Scherer.

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“The award was given at the time. The first drug based on this idea, it was approved for use in 2011. Patients treated for seven years, and we see the long-term consequences, they are more compelling,” said Sherra.

It is really so. Immune “brake” – that’s how experts describe the operation of open proteins – has a rich history. Both of the winner, as already mentioned, studied the structure of the immune system. Its fundamental feature – the ability to distinguish “their” from “alien” before destroy “them.”

Scientists knew that the recognition of the “enemy” meet the T-cells of the immune system – about 100 million different T cells travel around our body and look for abnormal cells. Receptor (red dot in the figure) is responsible for recognizing foreign cells. Co-receptor (designated in yellow) accelerates the process. However, this is not the whole system. Allison found that the system of CTLA-4 operates as a brake. It interacts with the “accelerator” and deprives the immune system of the ability to act.

Initially, this mechanism was studied in connection with autoimmune diseases. However, Allison developed an antibody that blocked CTLA-4. The hypothesis that this lock will free up T-cells to fight cancer cells, was confirmed by the experiment in 1994 in the laboratory of Allison at Berkeley. It was experiments on mice, to promote the necessary technologies were already partners in the field of medicine.

In a few years, a small biotechnology company agreed to produce similar antibodies to the human, a little later began clinical trials. In 2011, it was approved the first drug for inoperable metastatic melanoma. Regardless Ellison, 1991 at Kyoto University Honjo discovered the protein PD-1. Initially he did not know his functions, but later it turned out that he works as a brake, but a little different way. Honjo also turned to pharmaceutical industry and therapy on the basis of antibodies to PD-1 was approved for melanoma in 2014 (two drugs).

All the rest is history. In 2015 was approved two more drugs from melanoma, one from lung cancer, one from kidney cancer. In 2016, followed by Hodgkin’s lymphoma, bladder neck, and after development of the avalanche began. Clinical studies and withdrawal of drugs on the market to business, it is not a science, he told Allison in his lecture, 2017.

Allison emphasizes that his research was originally motivated by pure scientific curiosity – to understand how the immune system. And only after the fundamental discovery he proposed a practical use.

“Without basic research we would have nothing to transfer market, in the business. It would be good to allocate money for science in the National Institute of health and others had it in mind,” – said the scientist.

Cancer immunology is a rapidly developing area, and award winning therapy is not its only achievement. However, experts note that other methods are not so convincing. They either show the results only on laboratory animals but not on humans, or not give a convincing and reproducible results.

In addition, any manipulation of the immune system fraught with not always predictable and controllable consequences. “Most of the toxicity stems from the fact that the immune system begins to work “without brakes” and may not stop at the destruction of tumor tissue (which, in General, quite similar to the body’s cells), but also to begin to destroy its own healthy cells, which leads to damage of tissues and organs. Application oncoimmunology drugs can cause such serious complications such as autoimmune hepatitis, nephritis (inflammation of the kidney tissue), and thyroiditis (inflammation of thyroid tissue) and others. These inflammation is not due to an external impact, and work hyperactivemenu immune system, aimed to their own cells,” explains medical oncologist, a resident of the Higher school of Oncology Pauline Shyla.

Prize in physiology or medicine is one of the five prizes established by Alfred Nobel: the prize is awarded for outstanding achievements in chemistry, physics, literature, physiology or medicine for his contribution to peace. The first Nobel prize in physiology or medicine was awarded in 1901. The Russians have won this award only twice – it was Ivan Pavlov (for his work on the physiology of digestion) and Ilya Mechnikov (for his work on immunity). Both awards were received over 100 years ago.

This week will be announced and other Nobel prize winners 2018 – Tuesday physics Wednesday chemistry, on Friday the peace prize. This year due to reputational scandal in the Committee of the Nobel prize for literature be awarded will not.

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