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Tang Prize Laureate Dinarello Delivers Speech at EB
–Revealing EMA’s Approval of Anakinra for COVID-19 Treatment

The annual conference of Experimental Biology (EB), the world’s largest congregation in life sciences, will take place for four continuous days starting April 2 in Philadelphia, USA. It is an occasion where tens of thousands of scientists, researchers and educators gather together to explore the latest discoveries and trends in anatomy, biochemistry and molecular biology, investigative pathology, pharmacology, and physiology. One of the most important events in this year’s conference, the Tang Prize Award Lecture, is delivered by Dr. Charles Dinarello, one of the three winners of the 2020 Tang Prize in Biopharmaceutical Science.

The annual conference of Experimental Biology (EB), the world’s largest congregation in life sciences, will take place for four continuous days starting April 2 in Philadelphia, USA. It is an occasion where tens of thousands of scientists, researchers and educators gather together to explore the latest discoveries and trends in anatomy, biochemistry and molecular biology, investigative pathology, pharmacology, and physiology. One of the most important events in this year’s conference, the Tang Prize Award Lecture, is delivered by Dr. Charles Dinarello, one of the three winners of the 2020 Tang Prize in Biopharmaceutical Science. Titled “IL-1 as the Master Cytokine for Inflammatory Diseases,” this lecture features the exciting news that Anakinra, an anti-IL-1 biologic developed by Dr. Dinarello, has passed phase three trials and has been approved by the European Medicines Agency (EMA) for the treatment of COVID-19. There is also an introduction to a new oral biologic called OLT1177.  

The Tang Prize Award Lecture was introduced to EB in 2015, and Dr. Dinarello is the 7th Tang Prize laureate to give this lecture in the annual EB meeting. In a pre-recorded video that starts with introductory remarks by Dr. Shu Chien, president of the Tang Prize Selection Committee, Dr. Dinarello recalls his experience of studying interleukin-1 (IL-1) for more than four decades and talks about the therapies developed based on his research. He begins with the historical background of the medical community’s investigation of the relationship between infection and fever that was set in motion in 1943, the year Dr. Dinarello was born. He then enumerates members of the IL-1 family and draws special attention to the clinical development of biologics that block IL-1 and has succeeded in controlling many acute and chronic inflammatory diseases, such as autoimmune diseases, gout attacks, diabetes and cancer. He also mentions that because of the staggering number of tragic death caused by the coronavirus worldwide during the past two years, many efforts have been made to develop drugs to treat severe COVID-19. It has been found, after many clinical trials, that the recombinant IL-1 receptor antagonist (IL-1Ra), Anakinra can lower the rates of hospitalization, respiratory failure, and death by reducing COVID-induced inflammation, and help more patients fully recover from COVID-19. The EMA thus granted its approval. 

Dr. Dinarello expresses optimism about the future of the clinical application of IL-1 blockade. The rapid development of new drugs has enabled this therapeutic mechanism to be employed in the treatment of an increasingly broader range of diseases. Therefore, in this lecture, he also touches on a new oral biologic, OLT1177, an NLRP3 inflammasome inhibitor capable of effectively and safely reducing the level of IL-1βin patients with gout or systolic heart failure. Not having to depend on parenteral therapy is one of the great advantages this biologic offers. In conclusion, Dr. Dinarello believes that there is a bright prospect for cytokine biology, which began with the study of IL-1. He hopes those listening to his presentation will be inspired and more people will be motived to think about the importance of cytokine biology.  

The 2020 Tang Prize in Biopharmaceutical Sciences were awarded to three doctors who facilitated the development of cytokine-targeting biological therapies. America’s Charles Dinarello, Britain’s Marc Fledmann, and Japan’s Tadamitsu Kishimoto respectively discovered IL-1, TNF (tumor necrosis factor), and IL-6 (interleukin-6) and defined the crucial roles they play in mediating the body’s inflammatory response. Nowadays, many patients rely on biologics targeting these three cytokines for the treatment of various inflammatory diseases, including rheumatoid arthritis, ankylosing spondylitis, myocardial infraction, diabetes, and cancer. They have also been useful in reducing the number of people dying from severe COVID-19.   

In 1971, Dr. Dinarello started to purify leukocytic pyrogen from human white blood cells. It took him six years to identity two fever-inducing molecules, IL-1αand IL-1β. In 1977, he and his team published a paper in the Proceedings of the National Academy of Science, marking a significant milestone in cytokine research. In the wake of the failures of early experiments in humans, scientists shifted their focus from “injecting cytokines” to “inhibiting cytokines,” while it became clear to him that the overproduction of IL-1was a common cause of many diseases, and that IL-Ra  could inhibit IL-1αandβand block the signaling of IL-1R. Biologics that came out of this breakthrough understanding include Anakinra, Canakinumab, OLT1177, and so on. 

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