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Tang Prize laureates reflect on power of cytokine research

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Photo courtesy of the Tang Prize Foundation.

Taipei, Nov. 28 (CNA) The 2020 Tang Prize laureates for Biopharmaceutical Science reflected Saturday on the challenges faced and breakthroughs in their research related to cytokines that has helped many people fight inflammatory diseases.

Continuing the series of lectures delivered by the 2020 winners, American Charles Dinarello, British Marc Feldmann, and Japanese Tadamitsu Kishimoto all offered glimpses of how the understanding of cytokines has evolved and its effect on human health.

Cykotines are proteins produced by the immune system that transmit messages to various cells in the body and are contributors to inflammatory diseases, autoimmune syndromes, and cancers, roles that the three immunologists have helped uncover and counter.

Dinarello, 78, is considered "one of the founding fathers" of cytokines for his work in identifying the cytokine interleukin-1 (IL-1) and its role in causing fever and inflammation, despite initial skepticism in the scientific community.

Dinarello said the discovery of IL-1α and IL-1β, two fever-producing molecules, "was an important step in the history of cytokine biology."

After early experiments in humans, "the history of cytokines being used as a treatment changed dramatically" because it was clear IL-1 overproduction was a common cause of many diseases, Dinarello said.

The focus then shifted to "inhibiting cytokines, such as IL-1, such as TNF, such as IL-6," he said, which has led to the development of many therapies, including some based on the IL-1Ra (interleukin-1 receptor antagonist) protein.

IL-1Ra can inhibit IL-1αandβ and block IL-1R (interleukin-1 receptor) signaling, and Anakinra, a recombinant form of IL-1Ra, is now used to treat rheumatoid arthritis and prevent glycemic disorders in type 2 diabetes, he said.

Then there is canakinumab, an anti-IL-1β monoclonal antibody, that has been approved for treating a variety of diseases and could have a role in treating cancer, based on a clinical trial, he said.

Feldmann, 76, is known for identifying tumor necrosis factor (TNF) as the critical cytokine in rheumatoid arthritis and then developing therapies that combat TNF.

He said that roughly 50 percent of rheumatoid arthritis patients responded to anti-TNF therapy and the cancer drug methotrexate, but noted that "we've got a long way to go before every patient is cured."

TNF poses a challenge, he said, because TNF receptor-1 drives inflammation while receptor-2 does the opposite, meaning that if you block TNF entirely, you may be both blocking inflammation and preventing the body from dampening down the inflammation.

He and his colleagues are now "generating tools" that block TNFR1 without changing the function of regulatory T cells, he said.

Kishimoto, 82, is best known for his discovery and cloning of a cytokine, later named interleukin-6 (IL-6), that also contributes to the development of various inflammatory diseases.

In his talk, Kishimoto looked back at the research he and his team have carried out on IL-6 over the past 50 years, including how it was discovered and how it even ended up having relevance for treating COVID-19 patients.

"We discovered the overproduction of IL-6 has been found to be associated with many diseases, such as cardiac myxoma, Castleman's disease, rheumatoid arthritis, and systemic onset of juvenile idiopathic arthritis (JIA)," Kishimoto said.

To tackle the inflammatory responses provoked by IL-6 overproduction, Kishimoto and his team tried to treat patients by blocking IL-6 signals, and subsequently developed tocilizumab, an anti-IL-6 receptor monoclonal antibody.

It has since been approved for use in more than 100 countries for the treatment of rheumatoid arthritis and JIA, and also has proven effective in battling cytokine storms.

Kishimoto and team believed that tocilizumab could be effective in helping seriously-ill COVID-19 patients deal with cytokine storms, and large-scale clinical trials proved it could reduce the need for invasive ventilation or the risk of death.

Because of that, the United States Food and Drug Administration and the World Health Organization have both issued Emergency Use Authorizations for tocilizumab for the treatment of COVID-19 patients, Kishimoto said.

The three lectures were aired on the Tang Prize YouTube channel on Nov. 27, 2021.

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