Coronavirus Live Updates: New Research Boosts Evidence of Masks’ Utility, Some Experts Say

Coronavirus Live Updates: New Research Boosts Evidence of Masks’ Utility, Some Experts Say

  • July 28, 2020

The study, a Phase 3 clinical trial, will enroll 30,000 healthy people at about 89 sites around the country. Half will receive two shots of the vaccine, 28 days apart, and half will receive two shots of a saltwater placebo. Neither the volunteers nor the medical staff giving the injections will know who is getting the real vaccine.

Dr. Fauci estimated that the trial’s full enrollment of 30,000 will be completed by the end of the summer, and that results might be available by November. Even earlier results might be possible, he said, but added that he doubted that would be the case.

A second company, Pfizer, announced Monday afternoon that it would also begin a late-stage study of a coronavirus vaccine, on Tuesday. Pfizer has been working with a German company, BioNTech. Their study will also include 30,000 people, from 39 states in the United States, and from Brazil, Argentina and Germany.

The government announced last week that it had reached a $1.95 billion deal to buy 100 million doses of Pfizer’s vaccine by the year’s end, but only if the trial proves it safe and effective.

At the news briefing, Dr. Francis Collins, the director of the National Institutes of Health, said that at least three other Phase 3 trials would be starting soon, each needing 30,000 patients. Those trials will involve vaccines made by Novavax, by a collaboration of the University of Oxford and AstraZeneca, and by Johnson & Johnson. All are part of the U.S. government’s Operation Warp Speed.

Once volunteers are vaccinated, researchers will be looking for side effects and waiting to see if the vaccine significantly lowers cases of Covid-19. The study will also try to find out if it can prevent severe Covid-19 cases and death; if it can prevent infection entirely, based on lab tests; and if just one shot can prevent the illness.

Earlier tests of the vaccine showed that it stimulated a strong immune response, with minor and transient side effects like sore arms, fatigue, achiness and fever. But exactly what type of immune response is needed to prevent the illness is not known, so Phase 3 studies are essential to determine whether a vaccine really works.

Llama nanobodies block SARS-CoV-2 infection in vitro

Llama nanobodies block SARS-CoV-2 infection in vitro

  • July 15, 2020

The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is actively spreading across the globe, infecting more than 13.25 million people.

Now, a team of scientists at the United Kingdom’s Rosalind Franklin Institute may have a surprising solution for the coronavirus pandemic, which has killed more than 574,000 people worldwide.

Their research suggests that antibodies from llamas may provide immune-boosting therapy, which can help combat the ongoing coronavirus pandemic. The team used Fifi the llama’s specially evolved antibodies to generate immune-boosting therapy. Fifi is a 10-year-old llama that’s helping with experiments.

Llamas were chosen as they produce nanobodies, tiny antibodies which can be used in a clinical environment. The researchers used these nanobodies as they stick to the spike protein of the SARS-CoV-2.

Image Credit: Noe Besso

Image Credit: Noe Besso

Neutralizing effect

Llamas, camels, and alpacas naturally produce amounts of small antibodies and turn them into nanobodies. In the study, published in the Nature Structural and Molecular Biology, the team engineered the new nanobodies by using a collection of antibodies from llama blood cells. They found that the nanobodies were able to bind effectively to the spike protein of the novel coronavirus, blocking it from entering human cells through the angiotensin-converting enzyme 2 (ACE2), hence, and therefore blocking viral replication.

“This work establishes that nanobody maturation technology can be deployed to produce a highly neutralizing agent against an emerging viral threat in real-time. The approach may be useful in identifying complementary epitopes to those identified by animal immunization approaches,” the researchers wrote in the paper.


“The H11-H4 and H11-D4 nanobodies may find application in a cocktail of laboratory-synthesized neutralizing antibodies given for passive immunization of severely ill COVID-19 patients,” they added.

Future therapy

The team hopes that the experimental treatment could be used in a similar way to convalescent serum, which involves using the plasma containing antibodies from people who recovered from the coronavirus and transfuse it to those who are severely sick in the hopes they can have an immune boost to fight the infection. Convalescent plasma has been used to improve clinical outcomes by way of a process called passive immunization.

“These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping the progression of the virus in patients who are ill. We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone,” James Naismith, Director of the Rosalind Franklin Institute, said.

The team has currently started screening antibodies from Fifi taken after she was immunized with harmless purified virus proteins. The team is evaluating the preliminary findings, showing the llama’s immune system produced different antibodies from those already identified, which can provide many nanobodies to be tested against the virus.

Though the findings are promising, further research and evaluation are still needed.

What are the antibodies?

Antibodies are part of the body’s adaptive immune system. They are Y-shaped molecules that fight off infection by responding to invading viruses or bacteria by neutralizing them. After being exposed to a foreign substance, called an antigen, antibodies continue to circulate in the blood, protecting against future exposure to the specific pathogen.

It prevents future infection, and immune therapy can help boost a sick person’s immune therapy with antibodies that have already morphed to neutralize the virus.

The promising results may pave the way for therapies that can help patients stricken by the novel coronavirus to fight the infection, which can cause severe illness in vulnerable people. These include the elderly and those with underlying health conditions and immune system disorders.

COVID-19 global toll

The coronavirus pandemic has now affected 188 countries and territories worldwide, with the United States as the country with the highest number of infections. It has reported more than 3.41 million confirmed cases and more than 136,000 deaths.

Brazil has also reported skyrocketing cases over the past weeks, reaching a staggering 1.92 million cases and more than 74,000 deaths. South American is now one of the hardest-hit regions of the pandemic, with Brazil, Peru, and Chile reporting high infection rates. Peru has more than 333,000 confirmed cases, while Chile has reported at least 319,000 cases.

Other studies on immune therapy

In addition to this new research, other studies hint at the efficacy of nanobodies in neutralizing the SARS-CoV-2.

In China, a team of researchers at the Chinese Academy of Sciences report the efficacy of synthetic nanobodies in neutralizing the novel coronavirus pseudorviruses, which are synthetic viruses used to inject genetic material into bacterial and eukaryotic cells. These synthetic nanobodies show potential in the development of therapies to combat COVID-19.

In another study, a team of international scientists reported that two copies of a type of antibody produced by llamas could make a new antibody that can combat the coronavirus pandemic. The fragment found in a llama antibody can effectively bind to the proteins of the virus and neutralize it, akin to the effects of the other studies.

Lastly, a study showcased two copies of a special kind of antibody produced by llamas that can be used to make a novel antibody that binds tightly to a vital protein of the SARS-CoV-2, blocking infection.

All these studies point to one thing, nanobodies from llamas can potentially help in the development of therapies to fight infection with the SARS-CoV-2, and battle the current health crisis that has spread across the globe.

Sources:

Journal reference:

HIV research boosts race for coronavirus vaccine

HIV research boosts race for coronavirus vaccine

  • July 15, 2020


In 1984, scientists discovered the virus at the root of an alarming epidemic that was sickening otherwise healthy young men with aggressive cancers and rare, life-threatening pneumonias.

The discovery of HIV was a long-awaited moment, and Health and Human Services Secretary Margaret Heckler vowed that the scourge of AIDS would soon end. A vaccine would be ready for testing within two years, she proclaimed.

“Yet another terrible disease is about to yield to patience, persistence and outright genius,” Heckler said.

Thirty-six years later, there still is no HIV vaccine. But instead of being a cautionary tale of scientific hubris, that unsuccessful effort is leading to even greater confidence in the search for a coronavirus vaccine, from some of the same researchers who have spent their careers seeking a cure for AIDS.



Those decades of research on HIV have taught scientists an enormous amount about the immune system, honed vaccine technologies now being repurposed against the coronavirus and created a worldwide infrastructure of clinical trial networks that can be pivoted from HIV to the pathogen that causes the disease covid-19.

Laboratories, testing sites and recruitment networks that were rushed into action against the coronavirus exist because of the enormous amount of money spent on HIV. Equipment and expertise are in place. Infection control has been upgraded. Regulators are engaged.


“The investment in HIV research has made the response to covid-19 possible,” said Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, whose work on an HIV vaccine has led to one of the leading candidates for a coronavirus vaccine.


“Bring it on, we’re ready and waiting for the covid vaccine trials,” said Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Center at the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town in South Africa.

HIV is a devilishly complicated virus, deft at outwitting vaccine efforts, but there are real reasons to hope that the coronavirus will be a less resilient foe. Only by piggybacking on the HIV vaccine effort can coronavirus research move so fast.

“It’s really been a dramatic and rapid pivot for the people who are leaders in the HIV vaccine and prevention community,” said Nina Russell, deputy director for tuberculosis and HIV programs at the Bill & Melinda Gates Foundation.


Between 2000 and 2018, about $14.5 billion was spent on research toward an HIV vaccine, according to the Resource Tracking for HIV Prevention Research and Development Working Group, a project of the advocacy organization AVAC. Forty-six vaccines have survived to the preclinical or clinical stages of evaluation, and 100 were abandoned earlier in the process, the group’s data shows.

In contrast, there already are 160 vaccines under development for the novel coronavirus, a pathogen unknown to science a little more than six months ago, according to a list kept by the World Health Organization. Twenty-one of them are being evaluated in clinical settings. Billions of dollars have been committed by governments and private companies.

Now the two efforts are dovetailing.

“HIV has a lot of researchers in immunology and virology who set up labs, who have [vaccine] platforms, and they are looking to quickly repurpose to see if they can find a coronavirus vaccine,” said Meg Doherty, director of the WHO’s department of global HIV, hepatitis and STI programs.

– – –

Science is gambling that one or more of those efforts will yield and deploy a coronavirus vaccine within 12 to 18 months. Researchers are heartened by the key differences between the viruses. HIV integrates itself into the body’s cells, which means a vaccine has to start working immediately to rout the disease. People’s immune systems are not able to naturally defeat HIV, making a vaccine even more difficult to create. And it mutates much more quickly than the novel coronavirus, officially named SARS-CoV-2.

“It certainly won’t be easy, but what gives me hope is the natural history of this infection,” said Francis Collins, director of the National Institutes of Health. The large number of people who experience mild symptoms or none at all is a good sign that the immune system can defeat the virus.

“That’s different than HIV,” Collins said. “This is the kind of candidate where the vaccine should work. You know the immune system, given the appropriate priming, is able to eliminate the virus.”

Years of research on vaccines has helped scientists perfect technologies and methods that can be repurposed to the coronavirus, from RNA and DNA vaccines to those that use harmless viruses to deliver genes from the virus to cells.

Barouch, for example, has spent 15 years focused on HIV vaccine research. He developed a vaccine technology based on a harmless cold virus that could ferry specific genes into cells. Those genes code for a distinctive part of the AIDS virus to create an immune response.

The HIV vaccine based on that work, under development with the pharmaceutical giant Johnson & Johnson, was still being tested in clinical trials on a Friday in early January when Barouch was holding his annual lab retreat at Boston’s Museum of Science. A main topic of discussion was a new pneumonia in Wuhan, China, with 41 known cases and one death at the time.

The numbers seem small today, with more than 13 million cases confirmed around the globe, but Barouch and his laboratory found the news alarming even then. They decided they should do something.

That evening, the genome sequence of the virus was shared online by researchers in China, and Barouch’s lab began studying it. It didn’t take long to connect with a pharmaceutical partner, Johnson & Johnson, to work on a vaccine expected to begin human testing this month.

They repurposed the vaccine platform originally developed for HIV and Ebola by inserting genetic material that codes for the coronavirus’s distinctive spike protein. That should, in theory, trigger the immune system to develop coronavirus-fighting antibodies that protect people from infection. If it weren’t for HIV, Barouch said, his laboratory and its industry partner would not have been able to move so rapidly.

– – –

For years, the United States has built a large network to conduct the logistically complex clinical trials necessary to test HIV vaccines and preventive drugs. Larry Corey, a virologist and past president of the Fred Hutchinson Cancer Research Center in Seattle who is co-leading the Covid-19 Prevention Trials Network, said almost every aspect of running 30,000-person clinical trials for vaccines is built on the foundation of HIV.

That ranges from the data collection and biostatistics expertise needed to analyze large trials to the community relationships and experience in recruiting vulnerable people into complicated medical experiments.

The NIH unveiled its COVID-19 Prevention Trials Network on Wednesday. It is an amalgamation of several large clinical trial networks, two of them directly taken from HIV.

Leaders acknowledge that the challenges and scale are different this time: Not everyone is at risk of HIV, while the world population is vulnerable to the coronavirus.

Corey said that while a network might have spent years preparing to launch the trials now contemplated, it has to be done in only weeks.

The more mundane but essential aspects of clinical trials that ensure the results are unassailable are all in place: freezers that have been audited to show they never fail, personnel experienced at recruiting participants, operations managers accustomed to running years-long experiments.

“The NIH has invested a tremendous amount of money over the years in developing an international network capable of doing these types of trials, which requires a tremendous amount of infrastructure,” said Richard Novak, chief of infectious diseases at the University of Illinois at Chicago’s College of Medicine. “Fortunately they’re there and ready to go when something like this comes along. Otherwise, it would take years to develop.”

A critical lesson from HIV, the University of Cape Town’s Bekker said, is taking numerous approaches to a vaccine at the same time. HIV vaccine experiments often tended to be staged one after another, with the entire community waiting for the results of the best candidates. In contrast, numerous coronavirus trials are occurring simultaneously.

“If you want to do this quickly and you want to be sure you have a winner, then put a number of horses in the race that do a number of different things,” she said. And with the global population threatened, several safe, effective vaccines may be needed.

The world “may need more than one winner,” she said.

Leaders of the effort say years of experience engaging and building trust with minority, vulnerable and marginalized communities for HIV trials will help. But the coronavirus adds new complexities because of the speed and the scale of the trials. Older people in minority communities, for example, haven’t traditionally been the focus of HIV prevention trials, but they are a critical population to protect from the coronavirus.

“We’re going to need to be humble about the fact that we haven’t worked with some of these populations before,” said Nelson Michael, director of the Center for Infectious Diseases Research at the Walter Reed Army Institute of Research.

Four San Antonio institutions boost COVID-19 research projects

Four San Antonio institutions boost COVID-19 research projects

  • July 10, 2020

The San Antonio Partnership for Precision Therapeutics continues to boost the work of local scientists with research grants to study COVID-19.

In April, SAPPT funded University of Texas at San Antonio microbiologist Karl Klose’s research testing his “rabbit fever” vaccine on the coronavirus.

Liz Tullis, the partnership’s executive director, said Thursday that three additional projects will receive $200,000 each to learn more about the novel coronavirus

The four projects involve more than 20 researchers who work in labs at UT Health San Antonio, Texas Biomedical Research Institute, UTSA and Southwest Research Institute.

The research proposals considered are among several pitched that came with a promise of producing early results given the severity of the public health crisis.

COVID-19, the disease caused by the highly-contagious virus, has wrecked havoc on the American economy and led to a U.S. death toll of nearly 133,000. In San Antonio, at least 146 people have died after contracting the virus.

“This virus causes disease with varied effects, from asymptomatic and mild symptoms for some infected persons to more severe symptoms that require hospitalization and intubation in others. And of course, in some unfortunate cases, the disease may lead to the patient’s death,” said Adam Hamilton, president and CEO of SwRI.

“COVID-19 seems to impact some parts of our community harder than others,” he said.

Diako Ebrahimi and his team at Texas Biomed are studying the role of the protein FURIN in COVID-19 and why it might be deadlier in certain individuals, especially those with underlying cardiovascular conditions.

On ExpressNews.com: UTSA professor’s ‘rabbit fever’ vaccine tested against coronavirus

“While we’re talking about COVID-19 specifically in this research, the implications are much farther reaching,” said Dr. Larry Schlesinger, president and CEO of Texas Biomed. “We can use what we learn here and apply that knowledge to combatting the next novel coronavirus, HIV, and other infectious diseases. This study has a true precision therapy goal, as it aims to understand why certain individuals have greater severity of disease and why specific underlying conditions affect outcomes.”

Another research team, led by Dmitri Ivanov, a biochemistry and structural biology professor at UT Health San Antonio, is working to identify how people can bolster their natural immune system to counter COVID-19.

The goal is to identify antiviral compounds either among existing Food and Drug Administration-approved treatments or in libraries of drug-like molecules that could effectively combat the ability of the virus to evade a person’s immune defenses.

On ExpressNews.com: Four major San Antonio institutions bankroll new research program

Another UT Health San Antonio professor in the biochemistry and structural biology department received funding for his project, according to the announcement.

Yogesh Gupta and his team are studying how the virus evades the human immune system, by mimicking the host RNA and growing inside the body.

By understanding this process, he says the goal is to develop novel inhibitors that can block specific pathways that permit the virus to replicate inside the host cell and could pave the way to developing a new class of drugs to fight COVID-19, as well as other emerging coronaviruses

This most recent round of funding was made possible because of the San Antonio-based financial institution USAA, which has pledged to donate $1 million to organizations fighting COVID-19, and a nearly $100,000 donation to SAPPT from the San Antonio Area Foundation.

Laura Garcia covers the health care industry. To read more from Laura, become a subscriber. laura.garcia@express-news.net | Twitter: @Reporter_Laura

Combination therapy boosts the immune system's appetite for cancer

World’s first clinical trial of immune-boosting strategy to protect cancer patients from COVID-19

  • July 8, 2020

In the race to find new ways to prevent and treat COVID-19, Canadian researchers have launched an innovative clinical trial focussed on strengthening the immune system for one of the most vulnerable populations – cancer patients.

The trial involves IMM-101, a preparation of safe, heat-killed bacteria that broadly stimulates the innate, or “first-response,” arm of the immune system. The researchers hope that boosting cancer patients’ immune systems with IMM-101 will protect them from developing severe COVID-19 and other dangerous lung infections.

Researchers from The Ottawa Hospital came up with the idea for the trial and worked with the Canadian Cancer Trials Group (CCTG) at Queen’s University to design and run it in centres across the country. Funding and in-kind support, valued at $2.8 million, is being provided by the Canadian Cancer Society, BioCanRx, the Ontario Institute for Cancer Research, The Ottawa Hospital Foundation, The Ottawa Hospital Academic Medical Organization, ATGen Canada/NKMax, and Immodulon Therapeutics, the manufacturer of IMM-101.

“An effective vaccine that provides specific protection against COVID-19 could take another year or more to develop, test, and implement,” says Dr. Rebecca Auer, study lead, surgical oncologist and Director of Cancer Research at The Ottawa Hospital and associate professor at the University of Ottawa. “In the meantime, there is an urgent need to protect people with cancer from severe COVID-19 infection, and we think this immune stimulator, IMM-101, may be able to do this.”

“We know the immune systems of cancer patients are compromised both by their disease and the treatments they receive placing them at much higher risk of severe complications from COVID-19,” says Dr. Chris O’Callaghan, CCTG Senior Investigator, who will be overseeing this important national trial. “These patients are unable to practice social isolation due to the need to regularly attend hospital to receive critically important cancer treatment.”

The trial, called CCTG IC.8, has been approved by Health Canada and is expected to open at cancer centres across Canada this summer. People who are interested in participating should speak with their cancer specialist.

Additional quotes

COVID-19 has led to a quickly changing environment. Just as many businesses and organizations have had to adapt, some cancer researchers are also pivoting their work to address the unique challenges brought on by this pandemic. Thanks to the quick-thinking and innovation of Drs. Auer and O’Callaghan and with the support of Canadian Cancer Society donors, we are now able to conduct the world’s first clinical trial to prevent severe COVID-19 infections in people with cancer and help them live longer, healthier lives.”


Andrea Seale, CEO, Canadian Cancer Society

“This trial could support an important change to the standard of care for cancer patients by administration of IMM-101 prior to starting cancer treatment,” says Dr. John Bell, Scientific Director of BioCanRx. “Accelerating to the clinic, biotherapeutics that can enhance the quality of life of those living with cancer, is central to the BioCanRx mission.”

“There is a clear and urgent medical need for safe and effective ways to prevent SARS-CoV-2 infection and severe COVID-19 disease, especially for cancer patient populations,” says Dr. Thomas-Oliver Kleen, Chief Scientific Officer at Immodulon. “Immodulon is excited about this phase III trial and hopes that IMM-101 will provide increased protection against COVID-19 in these vulnerable patients.”

“OICR is excited to be collaborating on such a landmark clinical trial supporting cancer patients in this unprecedented time,” says Dr. Laszlo Radvanyi, President & Scientific Director of the Ontario Institute for Cancer Research. “IMM-101 may be an effective approach to protect our vulnerable patients not only against COVID-19, but also to boost their immune system to fight cancer.”

“Natural killer (NK) cells are the first line of anti-viral defense and, as such, a robust innate immune system and, in particular NK cell activity, is essential for protection against viruses such as SARS-CoV-2,” says Dr. Katia Betito, President of ATGen Canada/NK Max. “The possibility of boosting the immune system in high-risk patients such as those with cancer with a product like IMM-101 would be a major step in protecting this vulnerable population. We are excited to see whether our NK Vue test can provide a much-needed tool for the evaluation and follow-up of these patients.”

Aichi Cancer Center and NEC Launch Joint Research on Fundamental Study Aimed at Advanced Cancer Immunotherapy

Aichi Cancer Center and NEC Launch Joint Research on Fundamental Study Aimed at Advanced Cancer Immunotherapy

  • July 6, 2020

TOKYO, Jul 6, 2020 – (JCN Newswire) – Aichi Cancer Center(1) and NEC Corporation (NEC; 6701) today announced the launch of fundamental research aiming to realize the promise of advanced personalized cancer immunotherapy by improving the performance of NEC’s neoantigen prediction system and developing predictive biomarkers for patient stratification through the fusion of AI and experimental immunology.

This research aims to identify suitable neoantigen for vaccine use by using the neoantigen prediction system which NEC has been working on and the screening techniques using T cells for neoantigen from Aichi Cancer Center. In addition, this research aims to develop biomarkers for patient stratification using AI based on analytical data on a tumor immune microenvironment and clinical data.

The partners will realize the promise of advanced personalized cancer immunotherapy which boosts the immune system especially in combination with immune checkpoint inhibitors (ICIs).

Background

Although the ICIs showed a certain degree of therapeutic success in cancer therapeutics, the therapeutic effect is limited to few cases. Previous studies have suggested that there is a significant correlation between tumor neoantigen load and the clinical efficacy of ICIs. Accordingly, the immunotherapy could improve the therapeutic efficacy if the brakes on the immune system are disabled, and at the same time, the immune responses to neoantigens are accelerated. The important things for realizing effective cancer immunotherapies are 1.) the selection of neoantigens that harness the immune system and 2.) the patient stratification in treatment planning for ICI therapy, cancer vaccine therapy, and their combination therapy.

The Division of Translational Oncoimmunology at the Aichi Cancer Center has been conducting translational research using patient samples in collaboration with the departments of Thoracic Surgery and Thoracic Oncology at the Aichi Cancer Center Hospital. Specifically, this division specializes in experimental immunology and focuses on analyzing the immune microenvironment and the tumor-specific immune responses of each patient.

NEC is actively working on applied research in the drug development field using AI and has developed a unique AI-based neoantigen prediction system. NEC was accepted into the Tumor neoantigEn SeLection Alliance (TESLA) consortium given the uniqueness of this system and became the first Japanese company to join TESLA, founded and managed by the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute.

Outline of the Joint Research

1. Performance improvement of the neoantigen prediction system
Aichi Cancer Center and NEC will identify neoantigens recognized by T cells by using both the neoantigen prediction system and the immunological experimental approach. In the future, NEC will improve the performance of the neoantigen prediction system by using this high-quality data.

2. Development of biomarkers for patient stratification
Aichi Cancer Center and NEC will comprehensively analyze the tumor immune microenvironment of each patient. This research aims to develop biomarkers for patient stratification using AI based on clinical information, genetic mutation, gene expression, and experimental data obtained from the experiments described above.

Future Initiatives

Aichi Cancer Center will aim to carry out clinical trials of cancer immunotherapy. The clinical trials of cancer immunotherapy will be conducted at Aichi Cancer Center Hospital, and additional research will be conducted at Aichi Cancer Center Research Institute. The hospital and research institute will work together as a comprehensive cancer center.

NEC has been conducting applied research in the drug development field using AI for about 20 years. Through this joint research, NEC will accelerate its AI-driven drug development business by improving the performance of neoantigen prediction systems and developing biomarkers for patient stratification.

(1) Aichi Cancer Center
Designated by Japan’s Minister of Health, Labour and Welfare as a hub hospital for cancer genome medical care.
(2) NEC becomes the first Japanese company to join the TESLA consortium’s fight against cancer
https://www.nec.com/en/press/201905/global_20190514_01.html

About NEC Corporation

NEC Corporation has established itself as a leader in the integration of IT and network technologies while promoting the brand statement of “Orchestrating a brighter world.” NEC enables businesses and communities to adapt to rapid changes taking place in both society and the market as it provides for the social values of safety, security, fairness and efficiency to promote a more sustainable world where everyone has the chance to reach their full potential. For more information, visit NEC at https://www.nec.com.

Technical Contacts:

Aichi Cancer Center
Division of Translational Oncoimmunology
E-Mail: h.matsushita@aichi-cc.jp

NEC Corporation
AI Drug Development Division
E-Mail: contact@aidd.jp.nec.com

Copyright 2020 JCN Newswire. All rights reserved. www.jcnnewswire.com

Study reveals the role of glucocorticoid metabolism and GILZ regulation during aging

Study reveals the role of glucocorticoid metabolism and GILZ regulation during aging

  • July 2, 2020

Why do we age? What exactly is happening in our bodies? And can we do anything about it? Mankind has sought answers to these questions since time immemorial. While the pharmaceutical scientists Alexandra K. Kiemer and Jessica Hoppstädter from Saarland University are not claiming to have solved this ancient problem, they have uncovered processes within our immune system that contribute to aging. Kiemer and Hoppstädter have shown that low levels of the hormone cortisol and the protein known as GILZ can trigger chronic inflammatory responses in the body. The results have been published in the journal Aging Cell, doi: https://doi.org/10.1111/acel.13156

The phenomenon of human aging is the result of a complex interaction between numerous factors, with our own immune system playing a critical role. As we get older, our body’s own defense mechanisms age, too. The adaptive or specific immune system that each of us acquires over the course of our lives and that protects us from the pathogens that we came into contact with gradually deteriorates as we age. In contrast, however, our innate or non-specific immune system, which is the first line of defense towards a wide variety of pathogens, becomes overactive. The result is chronic inflammation.

A persistent state of inflammation can cause serious damage to our bodies. One consequence is that chronic inflammatory diseases, such as atherosclerosis or arthritis, are far more prevalent in older patients.

This has been well-known for a long time. In fact, the scientific community refers to this phenomenon as “inflamm-aging” – a portmanteau word that combines the two inseparably linked processes of inflammation and aging.”


Alexandra K. Kiemer, Professor of Pharmaceutical Biology, Saarland University

What was uncertain up until now was what actually caused these inflammatory responses to flare up. Kiemer and her research group have now provided some important insight. According to research results from Jessica Hoppstädter, a lead researcher in Kiemer’s team, the inflammatory process is linked to the fact that the amount of cortisol generated in the body decreases as we get older.

Cortisol and its inactive form cortisone, commonly referred to as stress hormones, are released by the adrenal gland. The hormone cortisol acts as a biochemical signaling molecule and is involved in numerous metabolic processes in the body. Cortisol deficiency in the body leads to an inflammatory response.

The serum level of cortisol in the body is lower in the elderly. Moreover, macrophages, an important type of immune cells, can convert inactive cortisone to active cortisol, but this ability declines with increasing age. What we observe is what we could call “macroph-aging” – the age-induced disruption of macrophage functions.”


Dr. Jessica Hoppstädter, Lead Researcher

Macrophages are important cells within the immune system that use signaling molecules to control other immune cells. They play a critical role in determining the extent of our body’s inflammatory response. However, macrophage function becomes impaired with increasing age. This can lead to an increase in the quantities of pro-inflammatory signaling molecules, which in turn drives the activity of other inflammatory cells of the body’s immune system.

The studies conducted by the pharmaceutical research team in Saarbrücken indicate that one particular protein is implicated in the malfunctioning of macrophages in the elderly. The protein is known as GILZ and its levels are regulated in part by cortisol. ‘The acronym GILZ stands for glucocorticoid-induced leucine zipper,’ explains Professor Kiemer. Kiemer’s research group has been conducting experimental studies on the GILZ protein for many years and has discovered that it plays a critical role in many important processes in the human body. But GILZ can have a beneficial or a detrimental effect depending on the specific metabolic conditions.

‘We know that GILZ plays a key role in our immune system, for example it’s involved in switching off the macrophage inflammatory response. So we put forward the hypothesis that loss of GILZ contributes to macrophage-mediated inflammation in older individuals,’ explains Jessica Hoppstädter. Her data shows that a lower cortisol level causes macrophages to produce less GILZ, which in turn means that the macrophages simply continue to release inflammatory signaling molecules. The team found that GILZ levels are indeed lower in older subjects. To find out whether that in itself was enough to cause an inflammatory response, Hoppstädter genetically deactivated the GILZ protein. The data confirmed Hoppstädter’s conjecture: the macrophages were activated and there was a resulting increase in chronic inflammatory processes.

Professor Kiemer’s research group is involved in a number of studies examining the activity of the GILZ protein, including the search for new active compounds that are capable of boosting GILZ levels in the human body. However, a substance able to arrest the progress of age-related inflammatory processes or impede macrophage aging is still a long way off. ‘All of these projects are still very much in the realm of basic research. The GILZ protein operates within an extensive network of complex biochemical interrelationships and it can have both beneficial and deleterious effects. A huge amount of work still needs to be done before we have a medically effective drug,’ says Alexandra K. Kiemer. The phenomenon of human aging remains immensely complex, but the work of the Saarbrücken scientists has moved us one small step further to a better understanding of why and how we age.

Source:

Journal reference:

Perez, J.V.V., et al. (2020) Altered glucocorticoid metabolism represents a feature of macroph‐aging. Aging Cell. doi.org/10.1111/acel.13156.

Age research: A low level of the stress hormone cortisol contributes to the ageing process

Age research: A low level of the stress hormone cortisol contributes to the ageing process

  • July 1, 2020

IMAGE

IMAGE: Why do we age? What exactly is happening in our bodies? And can we do anything about it? Mankind has sought answers to these questions since time immemorial. While the…
view more 

Credit: Iris Maurer

Why do we age? What exactly is happening in our bodies? And can we do anything about it? Mankind has sought answers to these questions since time immemorial. While the pharmaceutical scientists Alexandra K. Kiemer and Jessica Hoppstädter from Saarland University are not claiming to have solved this ancient problem, they have uncovered processes within our immune system that contribute to ageing. Kiemer and Hoppstädter have shown that low levels of the hormone cortisol and the protein known as GILZ can trigger chronic inflammatory responses in the body. The results have been published in the journal Aging Cell, doi: https://doi.org/10.1111/acel.13156

The phenomenon of human ageing is the result of a complex interaction between numerous factors, with our own immune system playing a critical role. As we get older, our body’s own defence mechanisms age, too. The adaptive or specific immune system that each of us acquires over the course of our lives and that protects us from the pathogens that we came into contact with gradually deteriorates as we age. In contrast, however, our innate or non-specific immune system, which is the first line of defence towards a wide variety of pathogens, becomes overactive. The result is chronic inflammation.

A persistent state of inflammation can cause serious damage to our bodies. One consequence is that chronic inflammatory diseases, such as atherosclerosis or arthritis, are far more prevalent in older patients. ‘This has been well-known for a long time. In fact, the scientific community refers to this phenomenon as “inflamm-ageing” – a portmanteau word that combines the two inseparably linked processes of inflammation and ageing,’ explains Alexandra K. Kiemer, Professor of Pharmaceutical Biology at Saarland University.

What was uncertain up until now was what actually caused these inflammatory responses to flare up. Kiemer and her research group have now provided some important insight. According to research results from Jessica Hoppstädter, a lead researcher in Kiemer’s team, the inflammatory process is linked to the fact that the amount of cortisol generated in the body decreases as we get older.

Cortisol and its inactive form cortisone, commonly referred to as stress hormones, are released by the adrenal gland. The hormone cortisol acts as a biochemical signalling molecule and is involved in numerous metabolic processes in the body. Cortisol deficiency in the body leads to an inflammatory response. ‘The serum level of cortisol in the body is lower in the elderly. Moreover, macrophages, an important type of immune cells, can convert inactive cortisone to active cortisol, but this ability declines with increasing age. What we observe is what we could call “macroph-ageing” – the age-induced disruption of macrophage functions,’ says Dr. Hoppstädter.

Macrophages are important cells within the immune system that use signalling molecules to control other immune cells. They play a critical role in determining the extent of our body’s inflammatory response. However, macrophage function becomes impaired with increasing age. This can lead to an increase in the quantities of pro-inflammatory signalling molecules, which in turn drives the activity of other inflammatory cells of the body’s immune system.

The studies conducted by the pharmaceutical research team in Saarbrücken indicate that one particular protein is implicated in the malfunctioning of macrophages in the elderly. The protein is known as GILZ and its levels are regulated in part by cortisol. ‘The acronym GILZ stands for glucocorticoid-induced leucine zipper,’ explains Professor Kiemer. Kiemer’s research group has been conducting experimental studies on the GILZ protein for many years and has discovered that it plays a critical role in many important processes in the human body. But GILZ can have a beneficial or a detrimental effect depending on the specific metabolic conditions.

‘We know that GILZ plays a key role in our immune system, for example it’s involved in switching off the macrophage inflammatory response. So we put forward the hypothesis that loss of GILZ contributes to macrophage-mediated inflammation in older individuals,’ explains Jessica Hoppstädter. Her data shows that a lower cortisol level causes macrophages to produce less GILZ, which in turn means that the macrophages simply continue to release inflammatory signalling molecules. The team found that GILZ levels are indeed lower in older subjects. To find out whether that in itself was enough to cause an inflammatory response, Hoppstädter genetically deactivated the GILZ protein. The data confirmed Hoppstädter’s conjecture: the macrophages were activated and there was a resulting increase in chronic inflammatory processes.

Professor Kiemer’s research group is involved in a number of studies examining the activity of the GILZ protein, including the search for new active compounds that are capable of boosting GILZ levels in the human body. However, a substance able to arrest the progress of age-related inflammatory processes or impede macrophage ageing is still a long way off. ‘All of these projects are still very much in the realm of basic research. The GILZ protein operates within an extensive network of complex biochemical interrelationships and it can have both beneficial and deleterious effects. A huge amount of work still needs to be done before we have a medically effective drug,’ says Alexandra K. Kiemer. The phenomenon of human ageing remains immensely complex, but the work of the Saarbrücken scientists has moved us one small step further to a better understanding of why and how we age.

###

The study

The study ‘Altered glucocorticoid metabolism represents a feature of macroph-aging’ provides insight into the roles of glucocorticoid metabolism and GILZ regulation during the ageing process. The publication was authored by researchers from the Department of Pharmaceutical Biology (Prof. Alexandra K. Kiemer) and the Department of Experimental and Clinical Pharmacology and Toxicology (Prof. Markus R. Meyer) at Saarland University, the Pharmacology Section, Dept. of Medicine at the University of Perugia (Italy) and from the Institute of Cardiovascular Regeneration at the University of Frankfurt. Aging Cell, doi: https://doi.org/10.1111/acel.13156

Questions can be addressed to:

Prof. Dr. Alexandra K. Kiemer

Pharmaceutical Biology

Tel.: +49 (0)681 302-57311 or -57322

Email: pharm.bio.kiemer@mx.uni-saarland.de

Dr. Jessica Hoppstädter

Pharmaceutical Biology

Tel.: +49 (0)681 302-57304

Email: j.hoppstaedter@mx.uni-saarland.de

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Regeneron identifies new combos to boost I-O drug Libtayo's cancer response

Regeneron identifies new combos to boost I-O drug Libtayo’s cancer response

  • June 24, 2020

PD-1/L1 inhibitors, which work by enhancing the immune response to cancer, have helped patients fight several types of tumors. But many individuals either don’t respond to these checkpoint inhibitors, or they eventually develop resistance to them.

Scientists at Regeneron were looking for ways to improve responses to PD-1 inhibitors, so they turned to bispecific antibodies that bridge the immune system’s T cells and tumor cells by binding to molecules present on cell surfaces.

In a new study published in Science Translational Medicine, Regeneron showed that adding bispecific antibodies targeting a T cell protein called CD28 to its Sanofi-partnered PD-1 inhibitor Libtayo led to enhanced anti-tumor activity in multiple animal models as well as long-term T-cell memory against the tumors.

Sponsored by Clinical Ink

White Paper: Keep Your GI Trials Moving During COVID-19

Clinical Ink’s intimate knowledge of and experience with GI trials enables a better deployment experience and improved trial conduct. Learn how our GI-specific data capture solutions can support virtual and hybrid trials during COVID-19.

Based on the encouraging early results, Regeneron hopes to have three CD28 costimulatory bispecifics in clinical tests by the end of 2020: REGN5678, a PSMAxCD28 bispecific for prostate cancer; REGN7075, an EGFRxCD28 bispecific for various growth factor receptor-related tumors, including non-small cell lung cancer; and MUC16xCD28 candidate REGN5668 for ovarian cancer.

If they succeed, these bispecific antibodies could serve as “off the shelf” T-cell boosters, Regeneron said.

For T cells to be fully activated, two signals are needed. In signal 1, T-cell receptors recognize a cancer protein. This paves the way for signal 2, in which costimulatory receptors, most powerfully CD28, cluster at the interface of T cells and target cells to enhance the T-cell activation. But by binding to PD-1 receptors on the T cell, tumor cells can suppress signal 2 by influencing CD28.

The Regeneron team figured that combining PD-1 checkpoint blockade with bispecifics targeting CD28 and tumor-specific antigens might solve the problem. The researchers tested the idea using two well-known tumor targets, PSMA and EGFR, for their CD28 bispecific antibodies.

In one mouse model of colorectal cancer, PSMAxCD28 or PD-1 blockade alone helped 15.6% and 12.1% animals survive, respectively, while the combination significantly improved survival to 70.8%. What’s more, the mice appeared to have generated long-term anti-tumor immunity, as the rodents were able to fight off a second tumor challenge without any additional combo therapy.

Similar effects were observed with a combination of an EGFRxCD28 bispecific and Libtayo in mice with human tumor implants. Both combinations also overcame resistance to PD-1 monotherapy.

RELATED: Safely overcoming resistance to checkpoint inhibition in cancer by blocking a growth factor

Targeting CD28 to supercharge T cells has been explored as an anticancer strategy. However, those efforts were largely shelved after an anti-CD28 superagonist triggered a severe inflammatory reaction known as cytokine storm in healthy people who volunteered for a phase 1 trial.

In Regeneron’s new study, the CD28 bispecific antibodies didn’t induce cytokine storm in monkeys. The bispecific antibodies don’t activate CD28 until they reach tumor cell surfaces, so they promote T-cell activation only at the tumor site, avoiding systemic toxicity, the researchers explained in the study.

Regeneron believes the animal studies prove that CD28 bispecifics have the potential to serve as a new, safer approach to enhance the therapeutic effects of immuno-oncology agents across various cancer types. First-in-human evidence is expected in 2021 from REGN5678, used in tandem with Libtayo, in patients with metastatic castration-resistant prostate cancer.

Adequate sample size, safety and pharmacokinetic studies crucial for success

Adequate sample size, safety and pharmacokinetic studies crucial for success

  • June 23, 2020

The discussion was held during the third NutraIngredients Immunity Online Series webinar, hosted by NutraIngredients-Asia,​ on the topic of ‘Botanicals and Immunity in APAC’. (Listen on demand here​)

The four-person panel consisted of Dr Stephan Plattner, business development manager at Iprona, Timothee Olagne, global category director at Naturex, Dr Dilip Ghosh, adjunct fellow at the Western Sydney Univeristy and Dr Lesley Braun, director at the Blackmores Institute.

It was hosted by Gary Scattergood, editor-in-chief of NutraIngredients-Asia.

In the botanical space, research in immunity has been growing in the last five years, so the discussion started off by finding out how the experts judged its quality and the scope for improvement.

Dr Braun began by explaining that for all studies in general, it was important to look at the methodology.

Within this, sample size was an area overlooked. She said an adequate sample size was necessary to demonstrate the findings.

Olagne agreed with the need for solid research with a large number of participants.

Dr. Braun added that particularly for botanicals: “It is also important to have clarity on the quality of extract being used and that the dosage used is adequate because not all extracts are the same​.”

Dr. Ghosh agreed and pointed out that it was necessary to conduct more pharmacokinetic studies on botanicals.

Doctors are still reluctant to prescribe these natural botanical medicines, but with more robust pharmacokinetic studies, it might be more accepting​.”

Do NOT follow this link or you will be banned from the site!