A special Tang Prize session in the 2021 Bio Asia-Taiwan conference, held on July 23 and hosted by Director Han-Chung Wu from the Academia Sinica, saw three winners of the 2020 Tang Prize in Biopharmaceutical Science talk about the journeys they embarked on more than half a century ago to study cytokines as well as the clinical applications that were discovered along the way. Dr. Charles Dinarello, distinguished professor of medicine at the University of Colorado, explored “The Broad Spectrum of Interleukin-1 in Inflammatory Disease”; Dr. Marc Feldmann, professor emeritus at Oxford University, spoke about “Anti-TNFα Blockade in Immunotherapy: Rheumatoid Arthritis and Beyond”; and Dr. Tadamitsu Kishimoto, former president of Osaka University, focused on the topic of “IL-6; from Arthritis to CAR-T and COVID-19.” In his closing remarks for this session, President of China Medical University Mien-Chie Hung made special reference to the Tang Prize in Biopharmaceutical Science and praised the contributions of these three laureates, before proceeding to deliver a speech on “Immune Checkpoint Therapy on Cancer.”
Recently, America’s Food and Drug Administration (US FDA) and the World Health Organization both granted Actemra ® (tocilizumab) an Emergency Use Authorization for the treatment of severe COVID-19 cases. This move once again drew the world’s attention to the role pro-inflammatory cytokines play in autoimmune diseases and sparked further discussions about this topic. Dr. Kishimoto began his lecture with an account of how IL-6 (interleukin-6) and its functions were discovered, and went on to illustrate why tocilizumab is effective in treating autoimmune diseases caused by the over-production of IL-6. Besides explaining how years ago he and his team developed tocilizumab, a recombinant humanized anti-IL-6 receptor antibody which has been contributing to the successful treatment of diseases such as rheumatoid arthritis and juvenile idiopathic arthritis, Dr. Kishimoto also referred to the fact that lately tocilizumab was found to be able to alleviate severe cytokine storm syndromes (CRS), a well-known complication of CAR-T cell therapy. Therefore, when the COVID-19 pandemic first broke out, he and his colleagues judged that this drug would work well against CRS induced by severe COVID-19 infection. Initial clinical trials supported this hypothesis and subsequent trials also confirmed that tocilizumab can reduce the probabilities of severe COVID-19 patients being intubated or dying from the disease.
Apart from the story about how he found and purified a leukocytic pyrogen later named interleukin-1 (IL-1), Dr. Dinarello also shed light on how IL-1 blocking therapies can be used to treat acute and chronic inflammatory diseases, such as post-myocardial infraction remodeling, diabetes, and cancer. He described how the inflammation in patients with type 2 diabetes was reduced after being administered with the IL-1 receptor antagonist. In addition, giving high-risk patients who had suffered a heart attack or stroke canakinumab, a monoclonal antibody targeting IL-1β, can lessen the chance of them having a second cardiovascular event. Outcomes of a large-scale trial show that canakinumab not only inhibits atherosclerosis for these patients but also significantly reduces the incidents of lung cancer. Dr. Dinarello concluded his talk by mentioning how early IL-1 receptor blockade was very efficacious in reducing the risk of death in patients with COVID-19-associated acute respiratory failure.
Anti-TNF (tumor necrosis factor) antibodies can be used to treat not only rheumatoid arthritis but also a variety of autoimmune diseases. They reshaped the world of antibody therapy and prompted more pharmaceutical companies to invest in the development of monoclonal antibody drugs, with one of the results being that sales of anti-TNF antibodies amounted to $25 billion in 2012. In his lecture, Dr. Feldmann revealed how TNF was identified as a therapeutic target, and pointed out that combining anti-TNF drugs and methotrexate can produce dramatically better responses in patients with rheumatoid arthritis. He also suggested the combination therapy of anti-TNF and anti-VEGF (vascular endothelial growth factor) as a way to get closer to a cure for rheumatoid arthritis. Another approach in predevelopment is to block a TNF receptor. TNF is known to have two receptors, TNFR1 and TNFR2. Choosing to block pro-inflammatory TNFR1 has potential to be more effective than blocking TNF. At the moment, an anti-TNFR1 antibody is in development in one of the companies Dr. Feldmann started.
Even though the pandemic has created many obstacles, the Tang Prize Foundation still believes that positive power can be generated through its global engagement. Thus, the Foundation continues to work with its laureates, urging people to face the problems that will jeopardize global sustainability and reminding them of the importance of a strategic approach to the reestablishment of social orders.
