Charles Dinarello (US), Marc Feldmann (UK/Australia) and Tadamitsu Kishimoto (Japan) were announced joint winners of the 2020 Tang Prize in Biopharmaceutical Science today (June 19) “for the development of cytokine-targeting biological therapies for treatment of inflammatory diseases."
Adding to Dr. Kishimoto’s joy of winning the prize with old friends Dr. Feldmann and Dr. Dinarello is the fact that the basic research they spent almost a century on has made a positive contribution to medical science and has even showed the potential to help patients suffering from Covid-19.
How can medications that treat inflammatory diseases also be used to combat Covid-19? Many patients with severe Covid-19 can be affected by the so-called “cytokine storm syndrome.” A cytokine storm is also an inflammatory reaction which occurs when the body’s immune system goes awry and releases an excess of cytokines that not only attack invaders but also start to set upon healthy cells, causing damage to body tissues and organs. Covid-19 is not the only disease that can turn our immune systems against ourselves. Another immune disorder which may cause serious complications and could be fatal is “autoimmune disease,” a type of inflammatory disease that can wreak mayhem in the daily life of 5-10% of the global population.
When little was known about cytokines, these three scientists carried out groundbreaking research which revealed their crucial roles as inflammatory mediators. Tumor necrosis factors (TNF), interleukin-1(IL-1) and interleukin-6(IL-6) are among the most investigated cytokines by the scientific community and biologics targeting them are among the most widely used biopharmaceuticals. The Tang Prize awardees have all made transformative contributions to the discovery and/or therapeutic development targeting these three cytokines.
Despite its name, the main job of tumor necrosis factors, as was found out later, is to regulate immune cells. Dr. Marc Feldmann, professor at the University of Oxford, was interested in the study of rheumatoid arthritis, which is one of the most common autoimmune diseases in the world. Dr. Feldmann was the first to demonstrate that diseased joints of those with rheumatoid arthritis have far more pro-inflammatory cytokines than normal, and identified TNF as the key one. After overcoming considerable skepticism, he finally convinced a pharmaceutical company to work with him and successfully developed an anti-TNF antibody that proved very effective against rheumatoid arthritis. The remarkable advance they made in the treatment of autoimmune and inflammatory diseases thus enabled patients debilitated by this degenerative condition to regain control of their lives.
IL-1 was the first cytokine to be identified and shown to be a central mediator of inflammation. Dr. Charles Dinarello, currently professor of medicine at the University of Colorado, is considered one of the founding fathers of cytokines and credited with the discovery and purification of the protein IL-1β, as well as cloning the gene encoded on it. Subsequently, another related protein was identified by other groups and named IL-1 receptor antagonist (IL-1Ra), which can block the biological activity of IL-1. A recombinant version of IL-1Ra was developed for the treatment of rheumatoid arthritis and later received FDA approval. These clinical achievements established IL-1 as potent mediators of fever and inflammation, led to the development of therapeutics for this important cytokine, and support Dr. Dinarello’s contributions to cytokine biology and the pathogenesis of inflammatory diseases.
Dr. Tadamitsu Kishimoto, professor at Osaka University, discovered and cloned IL-6, a cytokine that regulates antibody production. His group later identified and cloned its receptor and demonstrated the involvement of IL-6 in the pathogenesis of various inflammatory diseases. He then prepared a monoclonal anti-IL-6 receptor antibody and helped conduct large-scale trials on the efficacy and safety of the antibody in patients with rheumatoid arthritis as well as children with juvenile arthritis. Dr. Kishimoto’s work transformed the cytokine field and converted it from descriptive biology to modern molecular science and medicine. His work has also led to major clinical breakthroughs and development of new therapeutics for severe multi-organ chronic diseases. The contributions of Dr. Kishimoto encompass basic discovery, hypothesis forming, drug discovery and clinical translation, a true bench to bedside example.
In summary, the pioneering work of Drs. Feldmann, Dinarello and Kishimoto led to the development of biopharmaceuticals that have brought relief to millions of people tormented by autoimmune or inflammatory diseases.
All three cytokines are critically involved in the pathogenesis of a variety of diseases. Of special note is their critical roles in cytokine storms caused by Covid-19. Since biologics targeting the three cytokines respectively can inhibit cytokine actions, they have been either used successfully to treat cytokine storms in Covid-19 patients or are being investigated as a therapy, giving people much to hope for, at a time when the pandemic continues to rip through the planet.
Established by Taiwanese entrepreneur Dr. Samuel Yin, the biannual Tang Prize consists of four categories, namely Sustainable Development, Biopharmaceutical Science, Sinology and Rule of Law, with NT$ 40 million (approx. US$1.3 million) in cash prize and a research grant of NT$ 10 million (approx. US$0.33 million) allocated to each category. It aims to promote the interaction and cooperation between culture and technology so as to find a 21st century path to the sustainable development of the world. For more information, please visit the prize’s official website at https://www.tang-prize.org/en/first.php