The 2018 Nobel prize in medicine – immunotherapy for cancer

In 2018, the Nobel prize in medicine was awarded to the scientists James Ellisons USA and Tasuku Kodama from Japan. Thanks to their discoveries, we developed a new method of treatment of cancer. What is the essence of their work?

  • CANCER AND THE IMMUNE SYSTEM
  • BRAKES AND BOOSTERS FOR IMMUNITY
  • CTLA-4 TRAP FOR THE T-LYMPHOCYTES
  • PD-1 IS ANOTHER BLOCKER IMMUNITY

Cancer and the immune system

In some amazing way our immune system allows cancer cells to multiply uncontrollably. Latest simply evade immune surveillance, allowing them to behave as they want. From this moment begins the primary tumor, which then rapidly grows and develops, spreading to adjacent organs and metastases.

For the treatment of cancer is currently mainly used surgery. Operations effective at the stage when the cancer metastasized and has not penetrated to the nearest lymph nodes. In such circumstances, after removal of the tumor one may be fully recovered. Remission remains many long years, and a relapse may never occur. However, advanced stages of tumor disease are in need of more complex treatment with multiple sessions of chemotherapy and/or radiotherapy. In this scenario, the probability of relapse is high, and forecasts of doctors are unfavourable.

In the early 20th century proposed the concept that scientists should pay attention to your own immune system, which should become the main weapon against cancer. In those days of cancer patients even infected by pathogenic infection to enhance the immune system. However, these methods gave only a slight short-term effect.

Tasuku Honjo (left) and James Ellison

Brakes and boosters for immunity

Immune system a complex organism, consisting of individual organs, tissues, cells and macromolecular complexes. It’s a surprisingly well-honed mechanism by which the body is in a mode of constant protection.

Only when scientists put forward the concept of immune suppression of cancer tumors and many attempts proved futile, it became apparent that while physicians and scientists do not know enough about how it works immunity against the enemy.

Later scientists were able to determine the major players in the immune system that participate in the defense. This is the T cells a kind of white blood cells. That T-lymphocytes have specific receptors that bind to foreign substances, thus marking the latter. This allows the body to attract other cells of the immune system that will work for the destruction marked an outsider.

But the thing Why T lymphocytes do not work against cancer? What’s the mystery? Why they behave calmly, standing side by side with a cancer cell, which leads to death of the whole organism? The study of the mechanisms of T-lymphocyte has led scientists to the discovery of a specific class of substances, accelerators and brakes of T-lymphocytes.

Accelerate and brake are specific proteins that, by binding with T-lymphocytes can suppress or activate the immune system. A harmonious balance between brakes and accelerators allows the immune system to recognize and destroy strangers, not to touch her. It should be noted that too active immunity causes development of autoimmune diseases pathologies in which cells of the immune system begin to work against its own body cells. And so, to prevent this, there are brake.

БелокCTLA-4 blocks the T-lymphocyte

CTLA-4 trap for the T-lymphocytes

In 1990, the American scientist James Ellison in the laboratory of the University of Berkeley (California) studied one of the proteins of T lymphocytes CTLA-4. After a series of experiments, scientist came to the conclusion that the protein CTLA-4 acts on T-lymphocytes as a brake. It blocks the cells, not giving her a chance to perform its direct function.

Colleagues Ellison picked up his insights and began to use CTLA-4 to treat autoimmune diseases. And despite the fact that the results were good Ellison this aspect of the application of CTLA-4 were not interested. When he was working with this protein, he had the idea to use antibody to block to release T-lymphocytes from the trap to fight cancer cells.

Already in 1994, Ellison has put his first experiment on laboratory mice. The results are phenomenal! With antibodies to CTLA-4, which suppressed the inhibition of immune response of mice cured. Such anticancer therapy was very effective!

Protein PD-1 is another blocker of T-lymphocytes

PD-1 is another blocker immunity

Almost simultaneously with Jameson Allison, in 1992, a Japanese scientist, Tasuku Honjo discovered protein of T lymphocytes PD-1, which also acted as a brake for the immune system. Scientist conducted a series of studies in his laboratory at Kyoto University, thanks to which demonstrated that PD-1 inhibits the functioning of T-lymphocytes.

A few years later, a group of scientists under the leadership of Tasuku Honjo set up an experiment on animals, which showed that stopping PD-1 activates anti-tumor activity of T-lymphocytes, and it may become a promising direction in the fight against cancer.

In 2012, building on the work of Allison and Honjo, was made the first clinical studies on volunteers. The results were impressive. With drugs that block key brake, T-lymphocytes, in patients significantly increased the period of remission, and in some cases, such treatment led to complete cure even metastatic cancer.

Currently active work on improvement of cancer immunotherapy. It is noteworthy that this treatment is not without side effects in the form of an overactive immune system that can lead to the development of autoimmune diseases. However, the good news is that such processes are controlled.

Scientists Allison and Honjo were able to open a new era in the treatment of cancer, approximately the humanity close to total victory over cancer. This is, without a doubt, deserves this high award.

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