The 2020 Tang Prize in Biopharmaceutical Science went to Charles Dinarello (US), Marc Feldmann (UK/Australia) and Tadamitsu Kishimoto (Japan) “for the development of cytokine-targeting biological therapies for treatment of inflammatory diseases". The critical breakthroughs they made in their research not only advanced our understanding of three cytokines, namely tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6), but also revolutionized the way we treat inflammatory diseases.
Prof. Dinarello identified and cloned IL-1β, establishing IL-1β as a potent mediator for fever and inflammatory diseases, which led to the development of therapeutics for this important cytokine. Prof. Feldmann identified TNF as the key pro-inflammatory cytokine in rheumatoid arthritis and achieved groundbreaking success in blocking TNF with an antibody for the treatment of this disease. Prof. Kishimoto identified and cloned IL-6 and it receptor, and also developed an inhibiting antibody against the receptor, taking basic research all the way through to clinical application.
But why are cytokines responsible for causing inflammatory diseases? Academia Sinica Academician Hsing-Jien Kung illustrated the connection by drawing an analogy between cytokines and intruder alarms. When a burglar breaks into a house, it’s like an injurious agent breaking into our body. Sensing the danger, the alarm goes off to enlist help from security guards. In a similar way, cytokines will activate our immune system to get rid of the invading agent. However, when the alarm malfunctions and cannot be switched off, it will keep bringing in guards. Eventually not only the burglar, but also innocent people will get arrested. By the same token, when cytokines go into overdrive and cannot stop sending messages to the immune system, it will overreact and begin to attack healthy cells, thus evoking various inflammatory responses.
The 2020 awardees all made a great leap forward in the long history of research on these three cytokines as well as its practical application. They found the key targets in the pathogeneses of different inflammatory diseases. By aiming at these targets, biological therapies that are more effective and bring about less side effects can be developed, giving hope to people whose lives are being wrecked by these diseases.
When the immune system goes awry, cytokine storms can occur. They account for severe cases of infection experienced by 10% of Covid-19 patients and result in these patients developing severe pneumonia. The anti-IL-6 receptor antibody Prof. Kishimoto helped develop has benefited many tormented by autoimmune diseases such as rheumatoid arthritis. Moreover, in many clinical trials, it has also succeeded in preventing Covid-19-induced cytokine storms. He felt very proud that the basic research he has been conducting throughout his career can have such practical value at the time the world is engulfed in this pandemic.
On the other hand, in his acceptance clip, Prof. Feldmann mentioned that he has helped organize two trials, “one for intravenous anti-TNF patients in hospital, but also one for subcutaneous anti-TNF to keep patients out of hospital”. Though not knowing the result yet, he expressed optimism, partly because “patients already on anti-TNF but with IBD or rheumatological issues have a very good outcome.”
In a joint interview after the announcement, when asked about what motivated him to keep going, even knowing that all his efforts may not come to fruition, Prof. Kishimoto explained that he has always been interested in exploring the unknown. Being a doctor himself, he wants to know what is causing a disease in his patients and how to cure or prevent it. It brings him great joy seeing how his knowledge of the disease help relieve the pain his patients are racked with. His answer perfectly encapsulates the spirit of the Tang Prize in Biopharmaceutical Science: to commend those devoted to original basic research, and to reward them for the profound clinical significance the research has proven to have. For this reason, Prof. Dinarello, Feldmann and Kishimoto’s contributions to cytokine research and to the development of biologics that came along undoubtedly secure them a place in the pantheon of the Tang Prize.