The Tang Prize Foundation collaborated with Experimental Biology of the US and Taiwan’s National Cheng Kung University to stage the 2020 Tang Prize Masters’ Forum in Biopharmaceutical Science on 22 September on the university’s campus. While the three 2020 laureates, Dr. Charles Dinarello, university professor of the University of Colorado, Dr. Marc Feldmann, professor emeritus at the University of Oxford, and Dr. Tadamitsu Kishimoto, former president of Osaka University, were unable to travel to Taiwan for this event due to the pandemic, they delivered speeches, joined panel discussions and answered the audience’ questions via videoconferencing. Besides sharing their stories about their half-a-century research on cytokines and autoimmune diseases, they also shared their views with scholars and students in Taiwan and around the globe about the effects cytokine storms can have on patients with severe COVID-19 and the related clinical trials that are ongoing at the moment.
In her opening remarks, President of the National Cheng Kung University Huey-Jen Jenny Su reminded us of how these three laureates’ remarkable achievements ushered in the era of cytokine research, improved the quality of life for many patients, and allowed them to be hopeful of better treatment. Even though their groundbreaking discoveries were made decades ago, they still have profound influence on today’s biomedical research. Dr. Shu Chien, academician of Academia Sinica and president of Tang Prize Selection Committee, regretted that COVID-19 made it impossible for the latest laureates to come to Taiwan to receive the award in person, but believed that the forum would still be a great success as it provided a platform for the Tang Prize masters to have fruitful interactions with people on-site and online. Dr. William Coleman, representing the Experimental Biology, expressed his delight in having the honor to participate in the forum and also sent the 2020 laureates his heartfelt congratulations.
When the pandemic just broke out, the medical community immediately sought to gain a deeper understanding of how the immune system reacts to the novel coronavirus. Dr. Dinarello pointed out that from research papers he came across, “there was an indication that the cytokines were actually very high in this disease” and therefore it was speculated that “much of the pathology of the disease was actually coming from this large amount of inflammation due to the viral infection.” The inflammation could cause serious damage to our organs, and cytokine storms could “keep raging long after the virus is no longer a threat.” He and his team thus started studying cytokine storms induced by coronavirus and searching for potential therapies. At the moment, “there are 14 trials of anakinra in COVID-19 ongoing,” Dr. Dinarello informed us, and he is looking forward to the result of one particular “randomized placebo-controlled trial in Italy” that will “set a lot of issues.” He also holds optimistic views about the trials of REMAP-CAP, of the neutralizing antibody canakinumab, and of an oral inhibitor called OLT1177 that has been authorized by the US Food and Drug Administration.
Likewise, when COVID-19 began to emerge at the beginning of the year, Dr. Feldmann also began to explore whether anti-TNF could be potential therapeutics. Since experts in this field were not considering it, he wrote a paper published in The Lancet “documenting why it might be useful.” According to his summary, “there are relatively high levels of TNF” in patients with COVID-19, much higher than those in rheumatoid arthritis.” Moreover, “in databases of patients treated with inflammatory bowel disease or with arthritis of different types, the patients that are already on anti-TNF have a very good outcome if they get infected with COVID.” He will, of course, continue to examine other potential uses of anti-TNF. On the other hand, Dr. Kishimoto’s research on COVID-19 led him to the “in vitro study of vascular endothelial cells and cell activation,” which shows very high levels of IL-6, IL-8 and MCP-1. What’s interesting is that “the activation of endothelial cells induced very high plasminogen activator inhibitor-1 (PAI-1) so there is vascular damage. But tocilizumab anti-IL6R antibody completely suppressed IL-6, IL-8, and MCP-1, and also inhibited PAI-1 levels.”
Titled “Targeting the Hyperactive Immune System, from Autoimmune Disease to Cytokine Storms,” this forum was co-hosted by Prof. Yun Yen, president emeritus of Taipei Medical University, and Prof. Shaw-Jeng Sean Tsai, chair professor in the Department of Physiology at National Cheng Kung University. In addition to the lectures delivered by three 2020 awardees, 2014 Tang Prize and 2018 Nobel Prize winners Dr. James P. Allison and Prof. Tasuku Honjo also weighed in on how to regulate our immune response in accordance with each person’s biological individuality. For Prof. Honjo, the balance between releasing and inhibiting our immune cells is as delicate as that between yin and yang, and for Dr. Allison, when it comes to initiating or stopping T cell activation in order to treat cancer, how to achieve the optimal results hinges on how to best regulate our immune system.
Offering advice to young students sitting in the auditorium, Dr. Kishimoto encouraged everyone to commit themselves to basic research in order to bring clinical benefits to more people. Having focused on his research for almost half a century, he also emphasized the importance of perseverance because it can foster creation and imagination. Dr. Feldmann talked about how, when doing his PhD program, he learned to optimize tissue culture in immunology and how it subsequently sparked his interest in molecular mediators of immunity. When the new concept of targeting TNF as a potential therapeutic he proposed was not readily accepted in the medical community, his team still proceeded to carry out a series of experiments, and their hard work didn’t go to waste. Today, TNF inhibitors are usually seen on the list of the world’s blockbuster drugs. For Dr. Feldmann, to be able to relieve the symptoms for patients suffering from autoimmune diseases has been a source of joy and it also gave him a great sense of achievement. Dr. Allison highlighted the important role basic research plays in helping mankind find effective therapies, whether it is about treating autoimmune diseases or COVID-19. It proves that doing science is not only fun but can also actually help people. Dr. Dinarello hoped that aspiring young scientists can remain devoted to the project they chose, and don’t give up easily, because they never know “what nature has in store” for them. Dr. Honjo cautioned young people living in the age of information overload not to lose focus, and always remember to ask themselves what they want to know, not what they can do.
To watch the recording of this Masters’ Forum, please go to our YouTube website https://reurl.cc/Z7WE56
