Tang Prize Laureates Reflect on the Breakthroughs Made Possible by Cytokine Research 2021

Following the inspiring opening speech, “Future Perspective of Cancer Immunotherapy,” delivered by Nobel Prize and Tang Prize laureate Prof. Tasuku Honjo at the 14th Asia Pacific Federation of Pharmacologist Conference (APFP) on November 26, the 2020 Tang Prize Laureate’s Lecture for Biopharmaceutical Science, co-organized by the Tang Prize Foundation and The Pharmacological Society in Taiwan, took place at the 14th APFP at 1:30 p.m. (GMT+8) on November 27. Co-hosted by Dr. Wen-Chang Chang, chair of Taipei Medical University’s board of directors, and Dr. Yun Yen, chair professor at Taipei Medical University, this special session featured lectures delivered by three winners for the 2020 Tang Prize in Biopharmaceutical Science, Drs. Charles Dinarello, Marc Feldmann, and Tadamitsu Kishimoto, providing valuable informaiton on the role cytokines play in inflammation and the COVID-19 disease as well as possible treatments.

The first lecture by Dr. Dinarello, titled “Interleukin-1: The Prime Mediator of Systemic and Local Inflammation,” began with his purification of leukocytic pryogen from human white blood cells in 1971. It then took him six years to identify two fever-producing molecules, later named IL-1αand IL-1β. In 1977, the research outcomes were published in the Proceedings of the National Academy of Sciences, and for Dr. Dinarello, “that was an important step in the history of cytokine biology,” because many people in the field of life science were encouraged to study the immune system’s influence on human physiology. As a result, cytokine biology expanded rapidly. He also talked about how after the early experiments in humans, “the history of cytokines being used as a treatment changed dramatically,” and the focus was shifted to “inhibiting cytokines, such as IL-1, such as TNF, such as IL-6.” To help the audience understand the complicated network constituted by the pro-inflammatory molecules of the IL-1 family, Dr. Dinarello elaborated on the signal transduction of IL-1 family members, their pro- and anti-inflammatory characteristics, and the symptoms of different inflammatory diseases, so as to ease the way for the audience to get a proper grasp of the second half of the lecture which centered on “the clinical application of Il-1 blockade.” IL-1 overproduction, as Dr. Dinarello remarked, is a common cause of many diseases. IL-1Ra, on the other hand, can inhibit Il-1αandβ, and block the IL-1R signaling. Anakinra, a recombinant human IL-1Ra has been produced. It is used to treat rheumatoid arthritis and can also prevent glycemic disorders in type 2 diabetes. Moreover, canakinumab, an anti-IL-1βmonoclonal antibody successfully developed by Novartis, has been approved in a variety of diseases, ranging from rare hereditary diseases, rheumatic diseases, autoimmune and inflammatory diseases, to cardiovascular diseases. The most exciting news involving canakinumab is the clinical trial, CANTOS, which unexpectedly proved that canakinumab has an important role in treating cancer. Therefore, Dr. Dinarello believes that blocking IL-1 can usher in the dawn of a new cancer treatment.

The second speaker, Dr. Feldmann, shared his views on “Translating Molecular Insights in Autoimmunity into Effective Therapy.” The emphasis of the first half of his lecture was on how he discovered that anti-TNF can be effective in treating rheumatoid arthritis. Administrating either high or low doses of this drug can block TNF while also rapidly reducing the production of other inflammatory mediators. In their earlier experiments, Dr. Feldmann and his team demonstrated that around 50% of people with rheumatoid arthritis responded to the combination therapy using anti-TNF and the cancer drug methotrexate. That led him to believe that “we’ve got a long way to go before every patient is cured.” During the second half of the talk, Dr. Feldmann informed us that “TNF is a very unusual meditator, because it has two different targets: TNF receptor-1(TNFR1), which drives inflammation, and TNF receptor 2, which does the very opposite. So if you block all of TNF, you block of receptors. You block inflammation, but you also prevent the body’s attempt to dampen down the inflammation.” Therefore, he and his colleagues are “in the process of generating tools” and has already blocked TNFR1 without change the function of regulatory T cells. In addition, Dr. Feldmann mentioned the potential of anti-TNF for addressing many unmet medical needs, such as treating fibrosis of the hand by injecting anti-TNF into the palm. However, he pointed out the two obvious disadvantages of the anti-TNF he first developed: it was cost-prohibitive and “it was an injectable drug.” Thus, to develop “cheaper drugs that could be delivered by mouth” would bring greater benefit to the society. Throughout the lecture, Dr. Feldmann kept bringing up many people with whom he was or is collaborating for different projects and experiments, as he tried to drive home the message that what he had learned from these experiences was “how to work effectively with others” to ensure continuous breakthroughs in their research. It has been the hallmark of his career to find “talented people to work with,” and, “together with them,” to achieve much more “than we could alone.”

Presenting the third lecture on the topic “Interleukin-6: From Arthritis to CAR-T and COVID-19,” Dr. Kishimoto drew the audience’s attention to how IL-6 was discovered, why IL-6 is a pleiotropic molecule, and why IL-6 “is responsible for both antibody production as well as inflammation induction.” He also shed light on IL-6’s effects on autoimmune diseases and how IL-6 can trigger cytokine storms. Early on in his talk, Dr. Kistimoto made clear that the overproduction of IL-6 has found to be associated with many diseases, such as cardiac myxoma, Castleman’s disease, rheumatoid arthritis, and systemic onset of juvenile idiopathic arthritis (JIA). To tackle the inflammatory responses provoked by IL-6 overproduction, Dr. Kishimoto and his team tried to treat patients by blocking IL-6 signals. Subsequently, tocilizumab, a recombinant humanized anti-IL-6 receptor monoclonal antibody, was successfully developed and has been approved for use in more than 100 countries for the treatment of rheumatoid arthritis and JIA. With regard to how the production of IL-6 is regulated and why IL-6 overproduction often occurs in chronic inflammatory diseases, Dr. Kishimoto explained that the stabilization of IL-6 strongly depended on its messenger RNA. To rescue patients suffering from CAR-T cell-induced cytokine storms, many in the medical profession now will use tocilizumab to cushion the side effects of this therapy. In view of this example, Dr. Kishimoto and his team speculated that tocilizumab can also be effective in helping seriously-ill COVID-19 patients combat cytokine storms. Several large-scale clinical trials proved that it can lower the possibility of requiring invasive ventilation or the risk of death. For this reason, the US Food and Drug Administration and the World Health Organization have both issued an Emergency Use Authorization for tocilizumab for the treatment of COVID-19 patients. In this lecture, Dr. Kishimoto gave us a comprehensive overview of the research on IL-6 he led his team in carrying out over the past 50 years. It was a journey that took them from basic research to drug development and clinical application.

These three lectures by the 2020 Tang Prize laureates in Biopharmaceutical Science will be premiered on the Tang Prize YouTube channel from 4 p.m. to 7 p.m. (GMT+8) on November 27. To watch the complete version of the “2020 Tang Prize Laureate’s Lectures for Biopharmaceutical Science,” please consult the schedule below.

WHO urges countries to consider the benefits of vaccinating children against Covid-19, but prioritize sharing shots globally first

In a new interim statement, the World Health Organization on Wednesday called for nations to consider the benefits of vaccinating children and adolescents against Covid-19 — but to prioritize sharing vaccines globally before proceeding to vaccinate children.
“Countries should consider the individual and population benefits of immunising children and adolescents in their specific epidemiological and social context when developing their COVID-19 immunisation policies and programs,” said the statement, published Wednesday.
WHO has long argued that older adults, people with chronic health conditions and health workers should be prioritized for vaccines and that it is “less urgent” to vaccinate children. The new statement acknowledges that some countries that have already distributed vaccines to those prioritized groups, including the United States, are now rolling out vaccines to children.

The countries that are vaccinating children against Covid-19
The countries that are vaccinating children against Covid-19
In addition to the US and most members of the European Union, other countries vaccinating children include Cuba, which was the first country to vaccinate children as young as 2 starting in September, Chile, China, El Salvador and the United Arab Emirates.

“As a matter of global equity, as long as many parts of the world are facing extreme vaccine shortages, countries that have achieved high vaccine coverage in their high-risk populations should prioritize global sharing of COVID-19 vaccines through the COVAX facility before proceeding to vaccination of children and adolescents who are at low risk for severe disease,” WHO’s statement said. COVAX is WHO’s global vaccine sharing program.
“Given current global inequity in vaccine access, the decision to vaccinate adolescents and children must account for prioritization to fully protect the highest risk subgroups through primary vaccination series, and as vaccine effectiveness declines with time since vaccination, through booster doses,” the WHO statement said.
“As such, before considering implementing primary vaccination series in adolescents and children, attaining high coverage of primary series – and booster doses as needed based on evidence of waning and optimizing vaccination impact – in highest risk subgroups, such as older adults, must be considered.”
A push to vaccinate the world
WHO has long called for global vaccine equity.
In August, WHO pressed the 20 most powerful world leaders and pharmaceutical chiefs to reverse “disgraceful” inequity in access to vaccines by the fall.
WHO calls for world leaders and pharmaceutical chiefs to end ‘disgraceful’ global vaccine inequality
WHO calls for world leaders and pharmaceutical chiefs to end ‘disgraceful’ global vaccine inequality
Bruce Aylward, senior adviser to WHO’s director-general and head of the ACT Accelerator Initiative, said in an August social media Q&A that the world should be “disgusted” by the imbalance of available tools to fight the pandemic. He appealed to the world’s wealthiest nations to focus on helping all countries vaccinate 10% of their populations by September 2021.
That goal was not met, as “56 countries who were effectively excluded from the global vaccine marketplace were not able to reach the target of vaccinating 10% of their populations by the end of September — and most of them in Africa,” WHO Director-General Tedros Adhanom Ghebreyesus said in a news briefing last month.
Earlier in the pandemic, WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) issued a “roadmap” on how to prioritize Covid-19 vaccine supply starting with the most at-risk groups, an approach that has been adopted by most countries.
“I think whether children get vaccinated or not will depend a lot on, firstly, how we are able to cover these other priority groups first, what the epidemiology of the disease is,” WHO Chief Scientist Dr. Soumya Swaminathan said Wednesday at a news briefing in Geneva.
Millions of children worldwide missed routine vaccinations during the pandemic, study suggests
Millions of children worldwide missed routine vaccinations during the pandemic, study suggests
She added that more data is needed on children to better understand how much natural infection has occurred among their age group, something that will vary country by country.
“Then when we get to the goals of reducing transmission, really down to very low levels, at that point, one might consider, of course, vaccinating children as well,” Swaminathan said.
“I think the guidance on children will be very contextual and specific to local context,” she said. “But, we also need to then wait for more vaccines to have the data in children before we can make further recommendations.”
WHO notes in its new interim statement that there are benefits to vaccinating children and adolescents that go beyond direct health benefits, including that vaccinations can help keep schools safely open and decrease coronavirus transmission in other age groups, including older adults.
WHO also states that it is of “utmost importance” that children continue to get their recommended childhood vaccinations for other infectious diseases.
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In data published in July, WHO reported that 23 million children overall missed out on basic routine immunizations last year — which is 3.7 million more than who missed out in 2019.

“Even as countries clamor to get their hands on COVID-19 vaccines, we have gone backwards on other vaccinations, leaving children at risk from devastating but preventable diseases like measles, polio or meningitis,” Tedros said in the July announcement.
“Multiple disease outbreaks would be catastrophic for communities and health systems already battling COVID-19, making it more urgent than ever to invest in childhood vaccination and ensure every child is reached.”

Latest Updates Giving thanks during a pandemic: ‘We learn to appreciate things when we lose them’

In “Big Yellow Taxi,” the singer/songwriter’s jaunty 1970 tune about loss – of trees, of healthy food, of a love interest – she repeats and repeats, “Don’t it always seem to go / That you don’t know what you’ve got till it’s gone.”

Mitchell is challenging us to not take things for granted. There is a wildly simple way to do that. It’s called expressing gratitude.

Joni Mitchell has written a lot of great lyrics, but one line seems especially apt this Thanksgiving.

Sure, that may sound eye-rollingly New Agey. But in truth, there has never been a better time to be genuinely thankful than this holiday season, one that arrives in the throes of a wrenching two-year global pandemic. In fact, we as a society are uniquely poised to feel profound gratitude because of our tough times.

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Thanksgiving 2021 arrives amid an era of unprecedented hardship. Let’s not blow this chance to make gratitude a permanent part of our psyche.

If any parallel is apt, it is to those who grappled with the Great Depression. That generation faced a decadelong hardship so profound that it forged a lasting appreciation for the value of hard work and simple pleasures, both enshrined by the mythic paintings of Norman Rockwell.

“COVID-19 was all about death,” says Rice University historian Douglas Brinkley. “This recovery is about a renewed feeling of survival, a gratefulness for backyard barbecues, religious services, or listening to live music. It’s a time of gratitude.”

Consider this our Depression-lite Generation’s chance for an attitude makeover. Perhaps on Turkey Day, ditch those superficial appreciations (“I’m happy my football team won”) in favor of more profound celebrations (“I’m glad Grandpa Joe is here with us”). It’s simple enough, though it does take commitment.

The good news, those who study and lecture on gratitude tell USA TODAY, is that guides abound, from books to podcasts, on how to make time for gratitude. The practice not only makes you feel good but can even train the brain to keep that high alive, they say.

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The cautionary word, however, is that humans are prone to what’s called hedonic adaptation, which basically translates to a tendency to revert back to our old – and in this case, unappreciative – ways.

“We are very good at getting used to changes, good and bad, which is what adaptation is, so in that sense, gratitude is the antidote to adaptation,” says Sonja Lyubomirsky, psychology professor at the University of California, Riverside, and author of “The How of Happiness: A New Approach to Getting the Life You Want.”

In order to keep adaptation from erasing your sense of gratitude, “you need to commit to practicing it, consciously thinking or talking about what you appreciate about your life,” she says. “It’s work.”

But precisely because we have been toiling through a time of unprecedented hardship, experts urge us not to blow this chance to make gratitude a permanent part of our psyche.

“This pandemic is a huge opportunity for us as a society to reset because if you missed the memo, it’s still out there,” says Nancy Davis Kho, author of “The Thank-You Project,” a 2019 book in which she wrote 50 letters of gratitude to friends and family.

Through that yearlong process, Kho’s letters fortified her positive recall bias, which is “a tendency to notice good things around us, whether a good book or dinner or friend, and that rewires your brain so that it’s easier and easier to see those things in your life.”