Category Archives: Immunology

Immunology

As Chinese celebrate Lunar New Years Eve and coronavirus continues to spread @umich experts available to discuss health, economy, engineering…

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Jan. 24, 2020

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EXPERTS ADVISORY

Coronavirus: U-M experts can discuss

Mary Gallagher, professor of political science and director of the Lieberthal-Rogel Center for Chinese Studies, is an expert on Chinese politics, U.S.-China relations, labor and workers in China, and employment and labor law in China. She can discuss the political and economic implications of the travel lockdown on the eve of the Lunar New Year.

"The Chinese government response to the Wuhan Coronavirus crisis is like the 2003 SARS crisis, but sped up," she said. "This shows that the government realized its mistakes more quickly this time. What took months in 2003 took days in 2019.

"But still, for a resident of Wuhan or any large Chinese city, it must be confusing and infuriating that on the weekend the government reassured citizens that the virus did not spread between humans and was under control, and then, only four days later, to initiate an unprecedented lockdown of Wuhan and other cities on Thursday.

"It remains unclear if the early inaction was due to a lack of urgency, an inability to test people properly and quickly, or a desire to maintain a sense of stability before the Lunar New Year. Crises like this undermine people's confidence in the governments credibility and compassion."

Contact: 734-615-9154, metg@umich.edu

Herek Clack, associate professor of civil and environmental engineering at the College of Engineering, has studied airborne disease transmission and has developed a technologya nonthermal plasma reactorthat can remove and inactivate airborne pathogens by electrically charging them.

"We've tested it in our lab at the University of Michigan on a surrogate virus, proving that it's 99.9% effective at either removing or inactivating that virus," he said.

Clack can discuss the airplane environment, and the issues that surround contagions in the cabin air.

"All commercial aircraft have particulate filters in their cabin air treatment system. The problem is that viruses are much smaller than the smallest particles that typically can be captured on those filters. So, unless the virus is in, or on, a larger particle, it is unlikely that the virus by itself would be substantially removed as a result of being filtered by the typical passenger airplane filters."

Read a news release about his technology. Watch a video about his technology being tested for use in agricultural settings.

Contact: 734-763-6830, hclack@umich.edu

Aubree Gordon, associate professor of epidemiology at the School of Public Health, works on infectious disease epidemiology and global health, particularly the epidemiologic features and transmission of influenza and dengue fever. She is an investigator with the Centers of Excellence for Influenza Research and Surveillance.

"While the full extent of human-to-human transmission is still not known, Chinese authorities have verified multiple generations of transmission, meaning that transmission is clearly occurring in the community," she said. "This is worrisome as the easier it is for this virus to be transmitted, the harder it will be to control the outbreak.

"Initial reports suggest the severity of illness caused by this virus may not be as severe as SARS in 2002-03, however it is still very early in the outbreak and the true extent of severity is not yet known. We do know that it's causing severe lower respiratory disease in more than 20% of detected cases to date. What we don't know is if there are many more mild cases that occurred at the same time and were not detected."

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Contact: gordonal@umich.edu

Arnold Monto, the Thomas Francis Jr. Collegiate Professor of Epidemiology at the School of Public Health, is an internationally known expert on the transmission, prevention, mitigation and social response to outbreaks and pandemic planning including transmission modes. He has served as an adviser for the World Health Organization, consulted with the U.S. Department of Defense on communicable diseases, and visited Beijing during the SARS coronavirus episode in 2003.

Contact: 734-764-5453, asmonto@umich.edu

Howard Markel, the George E. Wantz Distinguished Professor of the History of Medicine at the Medical School and director of its Center for the History of Medicine, has studied epidemics over history and the effectiveness of efforts to contain their spread. He can speak on issues related to quarantine and travel.

His collaborative study with the Global Migration and Quarantine division of the U.S. Centers for Disease Control and Prevention on the 1918-19 influenza pandemic has played a major role in shaping the policies of the federal government, nations around the globe and the World Health Organization as they consider how to mitigate future pandemics. He is the author of "When Germs Travel: Six Major Epidemics That Have Invaded America Since 1900 and the Fears They Have Unleashed."

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Contact: Kara Gavin, 764-2220, kegavin@umich.edu

Emily Toth Martin, assistant professor of epidemiology at the School of Public Health, is an infectious disease epidemiologist with a focus on virus epidemiology and the use of vaccines and therapies to prevent and treat infection. Her research includes optimizing the use of diagnostics for viral diseases.

"We know this virus is a coronavirus," she said. "Other coronaviruses have caused very serious infections, like during the SARS outbreak, but some cause mild symptoms like the common cold. It's too soon to know how efficiently this virus is spreading between humans, or whether it is likely to die out on its own. There is a lot yet to learn about this virus, so public health officials are being cautious."

Video clipContact: 734-647-4723, etmartin@umich.edu

Theodore Standiford is a professor of medicine and interim chief of the Division of Pulmonary and Critical Care Medicine.

"Based on disease modeling, it is quite likely that the number of cases has been considerably underestimated and could be more than one thousand," he said. "In contrast to SARS-CoV and MERS-CoV, there has been no documented cases of individuals being infected outside of Wuhan, China, and no documented infections in health care workers caring for infected patients.

"Also, the risk for pandemic spread of the virus has been minimized by the early actions of the Chinese health authorities, WHO and CDC, including prompt closure of the site where the infection originated (fish and animal market in Wuhan City), systematic screening and quarantining of travelers departing from Wuhan and in destination cities nationally and internationally, and earlier and better adherence to contact and respiratory isolation precautions of infected subjects.

"Fortunately, the illness caused by 2019-nCoV appears to be less severe than that caused by SARS-CoV and MERS-CoV, coronaviruses which were associated with mortality rates of approximately 10% and 35%, respectively."

The Wuhan Novel Coronavirus: Should You Be Worried?

Contact: Kelly Malcom, 734-764-2220, kmalcom@umich.edu

Krista Wigginton is an associate professor of environmental engineering at the College of Engineering. Her research interests include the detection and fate of viruses in water and air, and on how to better control the environmental transmission of viruses. She led a 2015 study looking at the potential presence and fate of enveloped viruses in the urban water cycle, with emphasis on coronaviruses (e.g., SARS and MERS) and avian influenza viruses.

"The transmission of enveloped viruses, like coronaviruses and influenza viruses, is not usually associated with water; however sewage did play a role in some SARS coronavirus transmission," she said. "We need to anticipate the potential role of the urban water cycle in the spread of pandemic viruses, particularly for avian influenza viruses and coronaviruses. In order to address this, virologists, environmental engineers, and public health researchers must work together."

Contact: 734-763-9661, kwigg@umich.edu

Peter Jacobson, professor of health management and policy at the School of Public Health, can discuss the legal issues involving the spread of infectious diseases, including quarantine. His research focuses on the relationship between law and health care delivery, law and public health systems, and health equity. He has looked at previous cases including the 2014 Ebola outbreak, when several states imposed quarantines exceeding guidelines from the federal Centers for Disease Control and Prevention.

"As long as the screening is conducted in a nondiscriminatory manner and is limited in duration and scope, CDC appears to be acting appropriately under the circumstances," he said.

Contact: 734-936-0928, pdj@umich.edu

Joseph Eisenberg, professor of epidemiology at the School of Public Health, is an expert on infectious disease epidemiology and has 20 years of experience in microbial risk assessment work focused on water quality. He is part of a group of scientists from around the country who are involved with the Modeling Infectious Disease Agents Study, an NIH-funded program that focuses on infectious disease transmission modeling with a particular focus on waterborne pathogens. Their work has informed recent Ebola projections about infection rates and deaths.

Contact: 734-764-5435, jnse@umich.edu

Linda Lim, professor emerita of corporate strategy and international business at the Ross School of Business, focuses her research on the political economy of multinational and local business in Southeast Asia. That includes the changing international trade and investment environment, and the influence of domestic politics, economic policy and culture on business structure, strategy and operations.

Contact: 734-665-4803, lylim@umich.edu

Michael Imperiale, professor of microbiology and immunology at Michigan Medicine, studies virus replication, virus-host cell interactions and science policy. He serves as U-M's associate vice president of research-policy and compliance and has served on the National Science Advisory Board for Biosecurity, a presidentially commissioned advisory board, and on various policy-related committees of the National Research Council and the National Academies.

Adam Lauring is associate professor of microbiology and immunology, and infectious diseases, at Michigan Medicine. He studies RNA viruses, which include coronaviruses, evaluating their rapid mutation rate and implications for human disease. He collaborates with researchers at the School of Public Health to study how the influenza virus changes in home and clinical settings.

Contact: Kelly Malcom 734-764-2220, kmalcom@umich.edu

Sandro Cinti, professor of infectious disease at Michigan Medicine, is involved in preparation for bioterrorism and emerging infections at the national, state and local levels. In addition to treating infectious disease patients and training medical students and residents in the identification and care of infectious conditions, he helps lead biopreparedness activity at Michigan Medicine and coordinates with colleagues across the metro Detroit area and beyond.

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As Chinese celebrate Lunar New Years Eve and coronavirus continues to spread @umich experts available to discuss health, economy, engineering...

Immunology

PharmaForce International: New Product Launches and Additional Indication Approvals Lead to an Increase in Immunology Personnel – BioSpace

READING, Pa., Jan. 23, 2020 /PRNewswire/ -- PharmaForce International (PFI) recently completed a study that benchmarks the leading Immunology sales and marketing organizations in the United States. The report focuses on key companies with products competing across the Dermatology, Rheumatology, and Gastroenterology markets throughout 2019. Since the previous Immunology report published by PFI in 2018, the profiled companies have experienced a 25 percent increase in the total number of commercial operations personnel that are dedicated to Immunology. This includes various roles such as sales, marketing, field medical, market access, field reimbursement, and upper-level management.

Additional profiled company trends since the 2018 report include:

Joyce Wedemeyer, Director of Marketing and Sales at PharmaForce International, says that this increase in personnel is due to new product launches and additional indication approvals for existing products.

"The majority of these profiled companies have expanded their dedicated Immunology personnel in the anticipation of launching new products into the market or having additional indications approved. These expansions are strategic approaches to ensure better positioning versus the competitive products," says Wedemeyer.

PFI plans to further the focus on Immunology benchmarking in 2020. The United States Immunology report will be updated again, as well as a report on the five major EU countries. Both studies are expected to be completed and available to clients by December.

For more information on the reports mentioned above, please contact Joyce Wedemeyer at Joyce.Wedemeyer@strategicreports.comor by phone at 610-370-2906.

PharmaForce International (PFI) is a competitive intelligence firm with over two decades of experience in the pharmaceutical and biotech industries. PFI has become the market leader in commercial operations benchmarking and competitive intelligence.

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SOURCE PharmaForce International

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PharmaForce International: New Product Launches and Additional Indication Approvals Lead to an Increase in Immunology Personnel - BioSpace

Immunology

Key trends that will shaped the immunology market in the last decade, according to GlobalData – PharmiWeb.com

From an increase in sales of interleukin inhibitors to the prevalence of biosimilars, this decade has been an eventful one in the immunology industry.

Patrick Aiyes, Senior Immunology Analyst at leading data and analytics company GlobalData, observes the key trends that has shaped the immunology market in the last decade:

Key immunology drugs

The immunology market has seen a continuous increase in the sales of interleukin inhibitors and a decrease in the sales of TNF inhibitors - primarily because of the entry of biosimilars into the market and the increased safety profile associated with interleukin inhibitors. Abbvies Humira will end the decade as the highest grossing drug of 2019, generating sales of approximately $19bn globally, while Janssens Stelara will be the highest-grossing interleukin inhibitor in the market.

JAK inhibitors have also been a very popular drug in the immunology space. After the approval of Pfizers Xeljanz in RA in 2012, Eli Lillys Olumiant and Abbvies Rinvoq have followed suit. Although this class of drugs boasts a great efficacy profile and a fast onset of action, there has been controversy surrounding its safety and this has been a key topic in the latter years of the decade. Long-term studies are needed to see if this class of drugs will be useful in the next ten years.

Improvement in research

In the last decade, there has been a breakthrough in research surrounding diseases that have not had therapies approved. For example, in atopic dermatitis (AD) Sanofis Dupixient was approved in 2017, while Benlysta was approved for systemic lupus erythematosus (SLE) in 2011.

There have been many breakthrough and fast-track designations assigned by the US Food and Drug Administration (FDA) to promising drugs in diseases where there is a lack of safe and efficacious agents. Over the last ten years, graft versus host disease (GvHD) saw as many as nine drugs assigned breakthrough or fast-track designations, while AD saw six drugs, and SLE saw five. This is primarily because therapies with specific targets are now being introduced to help patients treatments.

Biosimilar disruption

The increasing prevalence of biosimilars has noticeably had a negative impact on mainstay biologics, including Janssens Remicade and Abbvies cash cow, Humira, which faced the introduction of biosimilars in Europe in 2018. In 2019, biosimilars will generate sales of over $3.4bn, with Pfizers Inflectra generating a whopping $671m.

On the disruption caused by biosimilars, big pharma is most at-risk from the arrival of biosimilar competition. However, many have invested in their own biosimilar pipelines to offset risk, typically through partnerships. Biosimilars were mainly brought in to help reduce the cost of very expensive drugs, while this strategy is working in Europe, there is still more to be done in order to keep healthcare costs low in the US.

About GlobalData

4,000 of the worlds largest companies, including over 70% of FTSE 100 and 60% of Fortune 100 companies, make more timely and better business decisions thanks to GlobalDatas unique data, expert analysis and innovative solutions, all in one platform. GlobalDatas mission is to help our clients decode the future to be more successful and innovative across a range of industries, including the healthcare, consumer, retail, financial, technology and professional services sectors.

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Key trends that will shaped the immunology market in the last decade, according to GlobalData - PharmiWeb.com

Immunology

Oxford Immunotec Announces Donation in Support of Coronavirus Testing Efforts to Help Differentiate Tuberculosis from the New China Virus – BioSpace

OXFORD, United Kingdom and MARLBOROUGH, Mass., Jan. 23, 2020 (GLOBE NEWSWIRE) -- Oxford Immunotec Global PLC (Nasdaq:OXFD) (the Company), a global, high-growth diagnostics company, today announced they are planning a new initiative to commemorate the coming World Tuberculosis Day, bring the benefits of the T-SPOT.TB test to mainland China and assist with differentiating tuberculosis (TB) from other respiratory infections. Oxford Immunotec will donate tests approximately valued at CNY 3,000,000 to Chinese hospitals through a non-profit organization, Bethune Charitable Foundation, in support of their efforts to combat the outbreak of the coronavirus.

Because some pathogens present with similar symptoms as TB, ruling out TB quickly in infected suspects is critical to fighting the spread of the infection. Since its approval in the Peoples Republic of China in 2010, T-SPOT.TB has been recognized for its high level of sensitivity and specificity across patient populations and has become a critical aid in the diagnosis of TB infection.

The donation plan is supported by leading hospitals and KOLs in China. Prof. Mou Xiangdong, Director of Respiratory and Critical Care Department, Beijing Tsinghua Chang Gung Hospital says, We would like to thank Oxford Immunotec for their commitment to the Chinese people. As symptoms of some infections may be similar to TB, this test will help us differentiate these illnesses with greater accuracy during epidemic seasons.

About T-SPOT.TB

The T-SPOT.TB test is available in over 60 countries and recognized by the World Health Organization (WHO) as one the 100 essential diagnostic tests that should be available in every country. In China, the T-SPOT.TB test has been on the market since 2010 and has been rapidly adopted by the leading hospitals and physicians as a critical tool for diagnosing TB infection. Today more than 250 of Chinas top hospitals rely on the T-SPOT.TB test to determine treatment for hard to diagnose patients. There is no comparable technology with similar sensitivity and specificity on the market in China. The T-SPOT.TB test is relied on as an essential tool in the fight against TB.

About Oxford Immunotec

Oxford Immunotec Global PLC is a global, high-growth diagnostics company focused on developing and commercializing proprietary assays for immunology and infectious disease. The Companys T-SPOT.TB test has been approved for sale in over 60 countries, including the United States, where it has received pre-market approval from the Food and Drug Administration, Europe, where it has obtained a CE mark, as well as Japan and China. The Company is headquartered near Oxford, U.K. and in Marlborough, MA. Additional information can be found at http://www.oxfordimmunotec.com.

CONTACTS:

For Media and Investor Inquiries: Matt McLaughlinChief Financial OfficerOxford ImmunotecTel: +1 (508) 573-9953mtmclaughlin@oxfordimmunotec.com

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Oxford Immunotec Announces Donation in Support of Coronavirus Testing Efforts to Help Differentiate Tuberculosis from the New China Virus - BioSpace

Immunology

L2P Research (Former AJES Life Sciences, LLC) and Transcell Oncologics, LLC Announce Partnership to Provide High Quality Hu-CB-CD34 and Hu-PBMC to…

ANNVILLE, Pa.--(BUSINESS WIRE)--L2P Research, LLC and Transcell Oncologics, LLC have entered into a partnership with the purpose of marketing and the distribution of Transcell Oncologics, LLC Trans HSC (CD34+), Trans-HSC (PBMC) product line and L2P Researchs humanized mouse models.

L2P Research, LLC is a Pennsylvania based Research organization founded with a vision to provide integrated R&D support in all the key areas of Pharmaceutical development. L2P provides a complete array of research services as required for Investigational New Drug Applications (IND). Transcell Oncologicss Transtoxbio portfolio (www.transtoxbio.com) is all about human sourced primary progenitor cell based predictive platforms that work for exploratory drug and cosmetics research meant for clinics.

The agreed terms of this partnership highlight the product line dealing with CD34+ cells and Humanized mouse models, the scope of joint business development utilizes both companys capabilities jointly to address demand, quality, fit with preclinical research grade stem cells ( For Academia, Pharma, Contract Research Organizations) in the USA.

CAT# TRANS-HSC-CBM; CAT#TRANS-HSC-CBCD34; CAT#TRANS-HSC-PBCD34Represent the CD34+ cells available lots.

CAT#TRANS-HSC-HMRepresent the humanized mouse models available to the user.

CD34+ cells and the cell based humanized animal models market is projected to reach $ 200 M by 2022 with their applications shown in Oncology, Immunology, Infectious Diseases, Neuroscience, Toxicology, and Hematopoiesis by the user.

This specific partnership between Transcell Oncologics and L2P Research is confident to address the existing gap seen between the demand and the quality of supply owing to respective groups advantageous positions and credibility dealing with right kind of cells and the animal models.

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L2P Research (Former AJES Life Sciences, LLC) and Transcell Oncologics, LLC Announce Partnership to Provide High Quality Hu-CB-CD34 and Hu-PBMC to...

Immunology

New Investments Expected To Boost The Z-drugs Market Between ‘ 2019’ And ‘2027’ Dagoretti News – Dagoretti News

Global Z-drugs Market Introduction

Nonbenzodiazepines, commonly referred as Z-drugs, are a widely prescribed class of psychoactive drugs for the treatment of different types of sleep disorders, particularly insomnia, which affects millions of people across the world. These drugs have similar effects as benzodiazepines by potentiating GABA (gamma-aminobutyric acid) activity in the body.

Global Z-drugs Market Competitive Landscape

Teva Pharmaceutical Industries Ltd., Sanofi, and Pfizer, Inc. are the major players operating in the global Z-drugs market. New product development and focus on emerging markets where the prevalence of insomnia is high are the strategies adopted by these players to increase market share.

Report Overview @https://www.transparencymarketresearch.com/z-drugs-market.html

Teva Pharmaceutical Industries, Ltd.

Teva Pharmaceutical Industries Ltd. is a key manufacturer of generic medicines and a recognized leader in innovative and specialty pharmaceuticals across the globe. The company delivers high quality and patient-centric health care solutions. It has a broad generics portfolio, with more than 1,000 molecules in nearly every therapeutic area. It continues to evaluate opportunities for joint ventures, collaborations, and other activities that support growth. Teva Pharmaceutical Industries focuses on establishing leadership position in its core therapeutic areas of respiratory (including asthma & COPD) and CNS through business development initiatives such as acquisition of Labrys Biologics in 2014 and Auspex Pharmaceuticals, Inc. in 2015.

Pfizer, Inc.

Pfizer, Inc. operates through two business segments: Pfizer Innovative Health and Pfizer Essential Health. The company has been issued 129 patents in the U.S. and 1,807 in the rest of the world for its products. It offers products in multiple therapeutic areas such as endocrinology, neurology, immunology, oncology, HIV, rare diseases, and hematology in more than 125 countries. Pfizer, Inc. has developed a strong supply chain network, which is directly responsible for addressing the patients needs. With technological advancements, the company tracks movement of products throughout the entire supply chain.

Sanofi

Sanofi is a global provider of health care solutions. The company has broad product portfolio that caters to areas such as rare diseases, multiple sclerosis, oncology, immunology, infectious diseases, diabetes, cardiovascular diseases, vaccines, and consumer health care. Sanofi focuses on acquisitions, in-licensing, and collaborations with key players in the market to reinforce its product pipeline. The company emphasizes on strategic reshaping of the product portfolio in order to strengthen its position in developed and emerging markets.

Global Z-drugs Market Dynamics

Large Patient Pool of Sleep Disorder Drives Demand for Z-drugs

Sleep disorder is a health concern for a larger percentage of the general population of the world. According to the Journal of Family Medicine and Primary Care, prevalence of sleep disorder is 10% to 30% of the global population, and insomnia in particular is on the rise. It is common in older adults, women, and people with medical and mental ill health. Such large population base of sleep disorder, especially insomnia, drives demand for Z-drugs.

Major Side Effects of Z-drugs to Hamper Market

Users of nonbenzodiazepines have reportedly experienced side effects such as short-term memory loss, sleepwalking, sleep driving, dizziness, headache, back pain, and rashes. This induces them to stop taking the drugs for long-term treatment, which in turn hampers sales of the drugs.

North America Dominated Global Z-drugs Market in 2018

According to the National Sleep Foundation, insomnia is the most common sleep disorder in the U.S. Moreover, around 40 million people in North America are affected by insomnia each year. The foundation also stated that prevalence of insomnia has increased among women and older adults in the region. Availability of drugs, high awareness about the effects of sleep disorder, and high prevalence of sleep disorders drive demand for Z-drugs in North America.

For More Details, Request A PDF Brochure Report @https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=71355

Global Z-drugs Market Segmentation

In terms of, the global Z-drugs market can be classified into:

Based on application, the global Z-drugs market can be categorized into:

In terms of distribution channel, the global Z-drugs market can be divided into:

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New Investments Expected To Boost The Z-drugs Market Between ' 2019' And '2027' Dagoretti News - Dagoretti News

Immunology

Surprising discovery could mean one-size-fits-all cancer treatment; researcher says nobody believed this c – OregonLive

Not so long ago, people had trouble even saying the word. They whispered it, with a shudder, or simply called it the C-word.

Treatments have come a long way from the days when a cancer diagnosis was a near-certain death sentence. Survival rates have dramatically increased in recent decades for many types of the disease.

Still, cancer remains fearsome and has resisted all attempts to eradicate it.

Now researchers at Waless Cardiff University have made a surprising discovery about the immune system they believe could lead to a pan-cancer cure. Their work indicates that a newly identified T-cell in the blood can be genetically modified, or reprogrammed, to kill a large variety of cancers without harming healthy tissue.

As the researchers put it in a peer-reviewed paper in Nature Immunology: the targeting of cancer cells would allow immune destruction of malignancies in all individuals.

Thats right -- all individuals.

It raises the prospect of a one-size-fits-all cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population, Cardiff University professor and lead author Andrew Sewell said in a university statement this week.

He added:

Previously nobody believed this could be possible.

Cancer experts not involved in the research say this is indeed an exciting development, with one calling it a transformative new finding. But they caution its early days. The process has been tested in the laboratory and in animals but not yet in humans.

At the moment, University of Manchester immunology professor Daniel Davis told the BBC, this is very basic research and not close to actual medicines for patients.

Whats unique about this newly discovered T-cell, Cardiff University said in a statement about the research, is that it sports a receptor that can recognize many types of cancer through a molecule called MR1 that, unlike previously known cell-surface molecules, does not vary in the human population -- meaning it is a hugely attractive new target for immunotherapies.

Sewell acknowledges there are plenty of hurdles to overcome, but he says the T-cell discovery opens up an exciting new frontier in the fight against cancer.

Read the research in Immunology Nature.

-- Douglas Perry

@douglasmperry

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Surprising discovery could mean one-size-fits-all cancer treatment; researcher says nobody believed this c - OregonLive

Immunology

Antiviral treatments inspire new kind of cancer drug | Stanford News – Stanford University News

Stanford virologist Jeffrey Glenn did not set out to tackle cancer. For years, he and his lab have worked to develop new ways of battling viruses like the ones that cause hepatitis delta and the common cold but the lessons theyve learned fighting viruses has led to a new kind of drug that has been effective at treating cancer in mice.

Jeffrey Glenn, professor of medicine and of microbiology and immunology, has spent years developing new ways to disrupt normal cellular processes in viruses. This work has led to drugs that can shrink and prevent the spread of tumors in mice. (Image credit: Courtesy of Stanford Medicine)

The underlying idea, Glenn said, is to disrupt otherwise normal cellular processes that both viruses and some cancer cells rely on to grow and spread. Now, tests in mice show that drugs based on that idea can shrink tumors and prevent their spread. The scientists from Stanford, the University of Texas, Baylor College of Medicine and the University of California, San Francisco, published their findings Jan. 22 in Science Translational Medicine.

Finding the new drug could not have happened without an unusual series of events and collaborations that spanned several academic disciplines, said Glenn, professor of medicine and of microbiology and immunology, whose lab developed the compounds with the assistance of Stanford ChEM-Hs Medicinal Chemistry Knowledge Center and support from ViRx@Stanford, an NIH-sponsored Center of Excellence for Translational Research led by Glenn.

Weve been working for many years on potent drugs that we had shown were important for viruses, said Glenn, who is also a member of Stanford Bio-X, the Maternal & Child Health Research Institute and ChEM-H. This is just an important target that hasnt really been appreciated in cancer, and we had the perfect drugs to get this started.

Originally, when they were looking for new ways to stop viruses such as hepatitis delta, Glenn and colleagues thought they might try a sort of end run around the virus and target cell functions that viruses hijack to replicate and spread. That way, even if a virus does infect a cell, thats more or less the end of it.

Glenns approach worked. In 2015, he and colleagues at the National Institutes of Health showed that the new approach prevented hepatitis delta from replicating and releasing new copies of the virus in patients. Later, they modified their strategy to attack enterovirus 71, which is best known for causing hand, foot and mouth disease but can also lead to devastating polio-like paralysis symptoms in children.

Glenn and his lab have continued to develop antiviral drugs, but their focus changed somewhat when their antiviral efforts caught the attention of Jonathan Kurie, a professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center. Kurie had learned that the same cellular processes Glenn and colleagues had successfully shut down was also involved in metastasis. After reading a paper describing the earliest compounds Glenn and his colleagues had developed, he wrote Glenn asking for some of the drug.

I told him we had much better molecules now, and we have known for a long time that they would also work in cancer, Glenn said, and he sent along two new compounds that he had developed with Mark Smith, who heads the Medicinal Chemistry Knowledge Center.

In the new paper, the team shows that their hunch was correct the same drugs Glenn, Smith and colleagues were developing to treat enterovirus can also treat certain kinds of cancers, at least in mice and human cancer cells in a lab dish.

In mouse studies, a drug the team tested reduced how often a human cancer implanted into the mouse in one lung spread to the second lung. With another compound, there were no detectable metastases at all, and both drugs reduced the size of tumors in the first lung. Human breast cancers growing in mice also shrunk in half after just one week of treatment.

The team also looked at an earlier drug developed in collaboration with Kevan Shokat, a professor of cellular and molecular pharmacology at the University of California, San Francisco, and a professor of chemistry at the University of California, Berkeley. That drug, they found, also curbed cell growth in human lung cancer cell lines. The team also gained some insight into which mice and one day, they hope, humans might benefit the most from the new drugs. They found that mice with extra copies of a particular gene responded much better to the drugs.

Now, Glenn said, My goal is to take this all the way to the clinic.

Glenn said the teams success is due in part to a significant shift in the last few years in what his lab does, building on an infectious brew of researchers from a range of academic disciplines.

I think thats the secret thing, having chemists physically in the lab with biologists, virologists and physician-scientists, Glenn said. Weve leveraged the special enabling environment of Stanford to create a unique group that has never existed before here or in academia. Its allowed things to happen that just wouldnt have happened otherwise.

That team is also starting to think about new ways to use their drugs, for example in combination with existing therapies to make them better against drug-resistant tumors, which might be susceptible to a new approach. Weve shown a proof of concept, and I think this could be useful in many cancers.

Additional Stanford authors are Edward Pham, a postdoctoral fellow in Glenns lab and a ChEM-H Physician-Scientist Research Fellow; Kaustabh Basu, a graduate student in chemistry; and research associates Khanh Nguyen and Grace Lam. Researchers from Baylor College of Medicine, the University of California, San Francisco, the University of Texas MD Anderson Cancer Center and the University of Texas Medical Branch contributed to the study.

The research was supported by grants from the National Institutes of Health, the Lung Cancer Research Foundation and the Department of Defense.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

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Antiviral treatments inspire new kind of cancer drug | Stanford News - Stanford University News

Immunology

supported scientists reverse HIV and SIV latency in two animal models – National Institutes of Health

News Release

Wednesday, January 22, 2020

Findings represent progress toward an HIV cure.

In a range of experiments, scientists have reactivated resting immune cells that were latently infected with HIV or its monkey relative, SIV, in cells in the bloodstream and a variety of tissues in animals. As a result, the cells started making copies of the viruses, which could potentially be neutralized by anti-HIV drugs and the immune system. This advance, published today in two papers in the journal Nature, marks progress toward a widely accessible cure for HIV.

The new research was conducted by investigators from the Collaboratory of AIDS Researchers for Eradication (CARE) based at the University of North Carolina at Chapel Hill and from the Emory Consortium for Innovative AIDS Research (E-CIAR) in Nonhuman Primates, both funded by the National Institutes of Health. Scientists from ViiV Healthcare and Qura Therapeutics collaborated on the research. CARE is part of the Martin Delaney Collaboratories for HIV Cure Research, the flagship NIH-supported HIV cure research program. The joint efforts of scientists from a variety of specialties made the new findings possible.

A simple, safe and scalable cure for HIV is an aspirational goal that, if achieved, would accelerate progress toward ending the HIV pandemic, said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. These new findings help sustain our cautious optimism that an HIV cure is possible.

While consistent antiretroviral therapy (ART) maintains the health of people living with HIV and prevents transmission of the virus, it is not a cure. Developing an HIV cure has been extremely difficult due to the persistence of viral reservoirs, where the virus hides from the immune system. These reservoirs consist of HIV-infected cells containing HIV genetic material that can generate new virus particles if a persons treatment is interrupted. The cells have entered a resting state that they maintain until they are activated to produce the virus. The immune system cannot recognize and kill HIV-infected cells in a resting state, and ART has no effect on them.

Consequently, scientists have been attempting to activate the HIV reservoir so therapeutic agents or an enhanced immune system can recognize and kill the infected cells, eliminating HIV. This strategy is often called kick and kill. Previous attempts to reactivate or kick the HIV reservoir worked well in the laboratory but were either ineffective or too toxic when tested in animals and people.

One of todays reports describes the testing of a compound called AZD5582, which belongs to a class of molecules that have proven safe as experimental cancer therapeutics.

CARE scientists obtained 20 mice with human immune systems, infected the animals with HIV, and then gave them ART that suppressed the virus. Next, the scientists injected AZD5582 into 10 of the mice and a placebo into the other 10.

Within 48 hours, high levels of HIV RNA were detected in the blood of six of the AZD5582-treated mice. HIV RNA levels in resting immune cells of the bone marrow, thymic organoid, lymph node, spleen, liver and lung were up to 24-fold higher in the AZD5582-treated mice than in the controls. This indicated that AZD5582 had activated resting cells in the HIV reservoir throughout the treated mice. The compound did not cause toxicity in the mice or activate their immune systems.

The E-CIAR and CARE investigators also obtained 21 rhesus macaques, infected them with SIV and gave them suppressive ART. More than a year after the monkeys began ART, the scientists gave 12 of them weekly intravenous infusions of AZD5582 for either three or 10 weeks.

The level of SIV increased in the blood of five of the nine monkeys (55%) that received 10 doses of AZD5582 and in none of the three monkeys that received fewer doses. Thus, SIV levels increased in five of 12 monkeys (42%) overall, even as they remained on ART. SIV RNA levels in resting immune cells from the monkeys lymph nodes were significantly higher in animals treated with 10 doses of AZD5582 than in the nine monkeys that did not receive the compound. The investigators found AZD5582 treatment to be safe for most of the monkeys. The scientists did not detect a consistent reduction in the size of SIV reservoir in the AZD5582-treated monkeys, however, suggesting that it may be necessary to pair the compound with another agent to kill activated reservoir cells.

The researchers have begun additional animal studies to determine the best dose and timing of treatment and to be sure AZD5582 activates the reservoirs of many different HIV and SIV strains. It also will be important to test other compounds in the same class as AZD5582 to determine which might work best in humans, according to the scientists. If the results of these follow-up studies are successful, a preliminary clinical trial of treatment with AZD5582 or a related compound in people living with HIV may follow.

This study was led by J. Victor Garcia, Ph.D., Ann Chahroudi, M.D., Ph.D., and Richard Dunham, Ph.D. Dr. Garcia is director of the International Center for the Advancement of Translational Science, an Oliver Smithies Investigator and a professor of medicine, microbiology and immunology at University of North Carolina at Chapel Hill. Dr. Chahroudi is an associate professor of pediatrics in the division of pediatric infectious diseases at Emory University School of Medicineand director of the Emory + Children's Center for Childhood Infections and Vaccines. Dr. Dunham is a director at ViiV Healthcare and an adjunct assistant professor at University of North Carolina at Chapel Hill.

The other new report published today describes how a combination of two agents strongly activated the SIV reservoir in ART-treated rhesus macaques and the HIV reservoir in ART-treated mice with human immune systems. One agent, an antibody called MT807R1, depletes the body of immune cells called CD8+ T cells. The other agent is an engineered protein complex called N-803, a more powerful version of a naturally occurring molecule that activates certain immune cells to fight pathogens.

E-CIAR scientists obtained 35 rhesus macaques, infected them with SIV and gave them ART, which suppressed the virus in 33 of the animals. At least a year after ART began, the scientists gave seven monkeys N-803 alone, 14 monkeys MT807R1 alone, and 14 monkeys both MT807R1 and N-803.

N-803 alone had no impact on the SIV reservoir. MT807R1 alone led to a moderate but significant increase in the level of SIV in the animals blood (their viral load). But the combination of MT807R1 plus N-803 led to a robust and persistent increase in the SIV viral load of all 14 animals even the six in which fewer than three copies of SIV were detected before the experimental treatment began.

CARE scientists at UNC replicated these outcomes in 23 mice that had been given human immune systems, infected with HIV and given suppressive ART.

In addition, investigators demonstrated in cell culture that N-803 could reactivate human immune cells latently infected with HIV, but that adding CD8+ T cells to the culture suppressed the latency-reversing activity of N-803.

Taken together, the findings illustrate that CD8+ T cells play a role in maintaining the SIV reservoir in monkeys. The scientists hope to clarify exactly how CD8+ T cells do this so they can develop a latency-reversing strategy that does not require eliminating all CD8+ T cells and is thus gentler on the body.

This research was led by Guido Silvestri, M.D. Dr. Silvestri is the Georgia Research Alliance Eminent Scholar in comparative pathology, professor and interim chair of the department of pathology and laboratory medicine at Emory University School of Medicine, and chief of the division of microbiology & immunology at Yerkes National Primate Research Center.

CARE is funded by NIAID with additional support from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, all part of NIH. E-CIAR is also funded by NIAID with additional support from the NIH Office of Research Infrastructure Programs.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

CC Nixon, M Mavigner et al. Systemic HIV and SIV latency reversal via non-canonical NF-B signalling in vivo. Nature DOI: 10.1038/s41586-020-1951-3 (2020).

JB McBrien et al. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells. Nature DOI: 10.1038/s41586-020-1946-0 (2020).

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supported scientists reverse HIV and SIV latency in two animal models - National Institutes of Health

Immunology

Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosi | TCRM – Dove Medical Press

Jean Kim,1,2 Robert Naclerio1

1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Medicine: Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence: Jean KimJohns Hopkins Bayview Medical Center, 4940 Eastern Ave, Suite A102B, Baltimore, MD 21224, USATel +1 410-550-0460Fax +1 410-550-2871Email jeankim@jhmi.edu

Abstract: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.

Keywords: chronic rhinosinusitis, nasal polyps, Type 2 inflammation, dupilumab

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Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosi | TCRM - Dove Medical Press