The 2018 Nobel Prize in Medicine recognizes the revolution in cancer treatment brought about by immunotherapy. It crowns 2 researchers: the American, James P. Allison, and the Japanese, Tasuku Honjo. Explanation.
In recent years, first in metastasized melanoma, then gradually in other solid tumors, immunotherapy has fundamentally revolutionized cancer treatment and saved patients who had hitherto been incurable. The Nobel Prize for Medicine, which was awarded on Monday to 2 researchers, crowns their efforts on 2 essential aspects of modern immunotherapy.
Classically, when we spoke of immunotherapy, we referred to the development of vaccines used to stimulate the immune system. But the responses to vaccination, very dependent on the antigen and the patient’s immune system, are often very variable, to the point of sometimes being dangerous. Modern immunotherapy is more targeted, more effective and better controlled.
New vision of immunotherapy
The work of these two researchers focused on deciphering the activation system of immune T cells that control the immune response, and on removing the “brakes” put in place by cancer to prevent this immune system from defending the body. against him.
The 2 researchers provided a better understanding of the role of 2 proteins on the surface of immune cells, T-CD4 lymphocytes. Their work now makes it possible to strengthen the immune defenses of patients suffering from cancer (which are always reduced) and to attack cancer cells in different types of solid tumors, the first being melanoma, the prognosis of which has been transformed at the advanced or metastatic stage. .
A life dedicated to cancer
James P. Allison, current chairman of the Department of Immunology at the MD Anderson Cancer Center, initially carried out his work at UC Berkeley in the 1990s and then at Memorial Sloan Kettering Cancer in New York. He first worked on a protein on the surface of lymphocytes called PD-1 / PD-L1, or checkpoint inhibitor. This is a protein that was initially identified as a brake on the immune system, and is actually a protein that the cancer cell uses to camouflage itself.
While working on understanding how T lymphocytes work, Allison actually discovered that by blocking this PD-1 / PD-L1 protein, cancer cells “in the eyes” of T lymphocytes were unmasked and an immune response became possible again. against this cancer.
Initially tested in advanced stage melanoma, PD-1 / PD-L1 inhibitors are revolutionizing cancer treatment by attacking lung cancer, bladder cancer, mesothelioma … in advanced stages such as now , in the earliest stages.
Another way to strengthen defenses
Tasuku Honjo works at Kyoto University in Japan, where he first studied another protein located on the surface of T cells known as CTLA-4. It has been identified as one of the cofactors involved in the activation / braking of T-CD4 lymphocytes, and more specifically as a brake on these cells. However, T-CD4 lymphocytes play a major role in activating the immune system.
Honjo then developed an antibody capable of neutralizing this protein and obtained spectacular results in stimulating the activity of T-CD4 lymphocytes and in cancer studies in mice. His work was relayed by Allison and his colleagues who demonstrated that mice with cancer could be cured by this antibody. Research continued until this drug, called “ipilimumab”, was adapted for humans and approved by the US Food and Drug Administration (FDA) in 2011 in patients with advanced melanoma. .
Two sides of immunotherapy
During this time, the development of anti-PD-1 continued and other molecules were approved successively. As monotherapy, anti-PD-1 treatments appear to be more effective than anti-CTLA-4 treatments, but the combination of the two is remarkably more effective, especially in melanoma. When these 2 types of immunotherapy are combined, CTLA-4, which stimulates immunity, and PD-1 / PD-L1, which prevents cancer camouflage, anti-cancer responses are better. In addition, when patients with melanoma have a prolonged response to treatment, it becomes possible to consider discontinuing the double immunotherapy without immediate relapse, which is not as often possible with treatment with a PD inhibitor. -1 in monotherapy.
All is not rosy
The combination of immunotherapies, however, increases the side effects, which become more severe and must be managed. Despite the wave of hope generated by these new treatments, not all patients can benefit from them yet: some cancers do not respond to these treatments, in particular those which are not very inflammatory and where there are few immune cells in the cancer. . In addition, these treatments are very expensive and jeopardize the financial balance of health insurance in the various countries.
Perspectives
There is still a lot of work to be done so that these new treatments can help more patients. Over the past 40 years, oncologists have perfected the handling of conventional cancer treatments such as surgery, chemotherapy and radiation therapy. Immunotherapy will not make them disappear and it is, on the contrary, necessary to develop the future good combinations of the various treatments to the best of the needs of each patient. The inclusion of immunotherapy when it is most useful will open up a whole new field of possibilities.
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