Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

Killer T cells that ‘remember’ past infection boost immune response to COVID-19 variants: Study

  • March 31, 2021

The killer T cell responses remained largely intact, as per the study, and could recognize virtually all mutations in the variants.

Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study

In this image, killer T cells surround a cancer cell. T-cells can ‘remember’ past infections and kill pathogens if they reappear. They are thought to have a big influence on how long people remain resistant to infection and disease. Image: NIH

The emergence of coronavirus variants has provoked concern about their impact on the effectiveness of vaccines, and whether people who were previously infected might be more susceptible to reinfection. But in welcome news, a new study on Tuesday showed that a key player in the immune response, called the “killer T cell,” remained mostly unaffected. The finding is encouraging because although these white blood cells are not a first line defense against infection, they can help prevent severe disease. Scientists at the National Institutes of Health and Johns Hopkins University analyzed blood samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of variants. They published their findings in Open Forum Infectious Diseases, an Oxford University Press journal.

The team wanted to know whether these cells, known by their technical name “CD8+ T cells,” could still recognize three variants of SARS-CoV-2: B.1.1.7, first found in Britain, B.1.351, identified in South Africa, and B.1.1.248, first seen in Brazil.

What makes each of these variants unique is the mutations they carry, especially in a region of the virus’ spike protein, structures that stud its surface and allow it to invade cells.

It has already been shown that mutations to this region of the spike protein make some variants less recognizable to neutralizing antibodies — infection fighting proteins produced by the immune system’s B cells.

This seems to be particularly true, for instance, of B.1.351, according to research on the impact of current generation COVID-19 vaccines.

Neutralizing antibodies are custom-made to fit an antigen, or a specific structure of a pathogen. In the case of the coronavirus , this is the spike protein, which the antibodies bind to, preventing the virus from infecting cells.

Killer T cells, on the other hand, look for telltale signs of cells that have already been infected with pathogens they have previously encountered, and then kill those cells.

In the new study, the researchers found that the killer T cell responses remained largely intact and could recognize virtually all mutations in the variants studied.

The researchers noted that larger studies are needed to confirm the results, but said that it nevertheless demonstrated that killer T cells are less susceptible to mutations in the coronavirus than neutralizing antibodies are.

Antibodies are still important to prevent infection in the first place — and the reduced efficacy of vaccines to the variants seems to be evidence of this.

But a killer T cell response that kicks in later and aids in clearing off the disease, helps explain why the vaccines seem to be able to prevent severe disease and hospitalization, even though their efficacy at stopping infection by variants is reduced.

Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

Killer T cells that ‘remember’ past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

  • March 31, 2021

The emergence of coronavirus variants has provoked concern about their impact on the effectiveness of vaccines, and whether people who were previously infected might be more susceptible to reinfection. But in welcome news, a new study on Tuesday showed that a key player in the immune response, called the “killer T cell,” remained mostly unaffected. The finding is encouraging because although these white blood cells are not a first line defense against infection, they can help prevent severe disease. Scientists at the National Institutes of Health and Johns Hopkins University analyzed blood samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of variants. They published their findings in Open Forum Infectious Diseases, an Oxford University Press journal.

The team wanted to know whether these cells, known by their technical name “CD8+ T cells,” could still recognize three variants of SARS-CoV-2: B.1.1.7, first found in Britain, B.1.351, identified in South Africa, and B.1.1.248, first seen in Brazil.

What makes each of these variants unique is the mutations they carry, especially in a region of the virus’ spike protein, structures that stud its surface and allow it to invade cells.

It has already been shown that mutations to this region of the spike protein make some variants less recognizable to neutralizing antibodies — infection fighting proteins produced by the immune system’s B cells.

This seems to be particularly true, for instance, of B.1.351, according to research on the impact of current generation COVID-19 vaccines.

Neutralizing antibodies are custom-made to fit an antigen, or a specific structure of a pathogen. In the case of the coronavirus, this is the spike protein, which the antibodies bind to, preventing the virus from infecting cells.

Killer T cells, on the other hand, look for telltale signs of cells that have already been infected with pathogens they have previously encountered, and then kill those cells.

In the new study, the researchers found that the killer T cell responses remained largely intact and could recognize virtually all mutations in the variants studied.

The researchers noted that larger studies are needed to confirm the results, but said that it nevertheless demonstrated that killer T cells are less susceptible to mutations in the coronavirus than neutralizing antibodies are.

Antibodies are still important to prevent infection in the first place — and the reduced efficacy of vaccines to the variants seems to be evidence of this.

But a killer T cell response that kicks in later and aids in clearing off the disease, helps explain why the vaccines seem to be able to prevent severe disease and hospitalization, even though their efficacy at stopping infection by variants is reduced.

Killer T cells boost immunity to coronavirus variants: study

Killer T cells boost immunity to coronavirus variants: study

  • March 30, 2021

Issued on: Modified:

Washington (AFP)

The emergence of coronavirus variants has provoked concern about their impact on the effectiveness of vaccines, and whether people who were previously infected might be more susceptible to reinfection.

But in welcome news, a new study on Tuesday showed that a key player in the immune response, called the “killer T cell,” remained mostly unaffected.

The finding is encouraging because although these white blood cells are not a first line defense against infection, they can help prevent severe disease.

Scientists at the National Institutes of Health and Johns Hopkins University analyzed blood samples from 30 people who had contracted and recovered from Covid-19 prior to the emergence of variants.

They published their findings in Open Forum Infectious Diseases, an Oxford University Press journal.

The team wanted to know whether these cells, known by their technical name “CD8+ T cells,” could still recognize three variants of SARS-CoV-2: B.1.1.7, first found in Britain, B.1.351, identified in South Africa, and B.1.1.248, first seen in Brazil.

What makes each of these variants unique is the mutations they carry, especially in a region of the virus’ spike protein, structures that stud its surface and allow it to invade cells.

It has already been shown that mutations to this region of the spike protein make some variants less recognizable to neutralizing antibodies — infection fighting proteins produced by the immune system’s B cells.

This seems to be particularly true, for instance, of B.1.351, according to research on the impact of current generation Covid vaccines.

Neutralizing antibodies are custom-made to fit an antigen, or a specific structure of a pathogen.

In the case of the coronavirus, this is the spike protein, which the antibodies bind to, preventing the virus from infecting cells.

Killer T cells, on the other hand, look for telltale signs of cells that have already been infected with pathogens they have previously encountered, and then kill those cells.

In the new study, the researchers found that the killer T cell responses remained largely intact and could recognize virtually all mutations in the variants studied.

The researchers noted that larger studies are needed to confirm the results, but said that it nevertheless demonstrated that killer T cells are less susceptible to mutations in the coronavirus than neutralizing antibodies are.

Antibodies are still important to prevent infection in the first place — and the reduced efficacy of vaccines to the variants seems to be evidence of this.

But a killer T cell response that kicks in later and aids in clearing off the disease, helps explain why the vaccines seem to be able to prevent severe disease and hospitalization, even though their efficacy at stopping infection by variants is reduced.

Cancer Research Institute and RevImmune Announce Dosing of First Patient in New Phase 2 Study Assessing Therapeutic Benefit of Interleukin-7 in Patients with Cancer and COVID-19

Cancer Research Institute and RevImmune Announce Dosing of First Patient in New Phase 2 Study Assessing Therapeutic Benefit of Interleukin-7 in Patients with Cancer and COVID-19

  • March 30, 2021

NEW YORK and BETHESDA, Maryland, March 30, 2021 — The Cancer Research Institute (CRI), a nonprofit organization dedicated to the discovery and development of powerful immunotherapies for all cancers and RevImmune, Inc., a privately held biotech company focused on T-cell technology and development, announced today the dosing of the first patient in a new study designed to assess the therapeutic benefit of interleukin-7 (IL-7) in cancer patients with COVID-19. This stems from a new understanding that patients with severe COVID-19 have low levels of T cells and exhausted T cells, and these patients benefit from therapies that focus on augmenting the cellular immune response, rather than solely therapies that dampen the immune system.

The Phase 2 multi-center clinical trial called “ILIAD-7-US-O” will evaluate the clinical benefit of RevImmune’s product candidate CYT107 in approximately 48 patients living with cancer. CYT107 is a therapeutic form of the master growth factor for human T cells, IL-7, and this is the first study to test an IL-7 drug specifically in people with cancer who also have COVID-19. The clinical trial is funded by CRI’s Clinical Accelerator, a program that supports and coordinates early-phase clinical trials of promising immuno-oncology combination therapies.

“This partnership allows CRI to apply RevImmune’s promising IL-7 agent in a novel setting of patients with both cancer and COVID-19, potentially offering a way to strengthen the immune system’s ability to fend off the SARS-CoV-2 coronavirus, mitigate symptoms of COVID-19, and improve overall outcomes for people living with cancer and COVID,” said Jay Campbell, managing director of CRI’s Venture Fund and Anna-Maria Kellen Clinical Accelerator.

Common cancer treatment regimens can compromise a patient’s immune system, including reductions in lymphocyte counts, such as T cells, a condition known as lymphopenia. Similarly, COVID-19 can lead to dysregulation of the adaptive immune system, which can also result in patients becoming lymphopenic. The profound and protracted lymphopenia experienced in COVID-19 patients has been correlated with increased secondary infections and death. Furthermore, surviving lymphocytes have severely impaired anti-viral function and are exhausted, ultimately resulting in immune system collapse.

IL-7 has been shown to provide a rapid and durable restoration of functional immune cells, predominantly CD4+ and CD8+ T cells, which are able to fight the primary viral infection and secondary infections. In previous clinical studies, CYT107 has demonstrated the ability to quickly restore immune function, such as increasing the number and diversity of T cells in patients, including those with low and exhausted T cell levels. CYT107 has been shown to be safe and well-tolerated and patients experienced durable long-lasting responses.

Researchers involved in the ILIAD-7 study hope CYT107 will provide the same benefit to cancer patients with COVID-19, with the aim of reducing risk of progressing to severe stages of COVID-19.

“The medical community has learned a great deal about COVID-19 as a disease this past year and has come to realize that patients who develop severe COVID-19 symptoms have impaired immune systems, including exhausted and depleted T-cells,” said Michel Morre, D.V.M., M.Sc., chief scientific officer at RevImmune. “Therapies like IL-7 reinvigorate and expand the cellular immune response to the infection, and we are excited for the opportunity to continue to follow the science and evaluate a potential treatment option for those affected by both COVID-19 and cancer.”

About the ILIAD-7-US-O Study
The ILIAD-7-US-O study tests RevImmune’s recombinant interleukin-7 product, CYT107, on patients with cancer and lymphopenic (with low lymphocyte counts) COVID-19. The trial aims to compare the effects of CYT107 versus placebo at producing immune reconstitution by restoring lymphocyte function and increasing lymphocyte proliferation in oncology patients, where their cancer is being or has been treated with standard of care therapies. The trial hopes to observe a possible clinical improvement as patients with restored lymphocyte counts should better eliminate invading pathogens such as SARS-CoV-2. Approximately 48 patients will be randomized 1:1 to receive either CYT107 or placebo at two trial sites: Memorial Sloan Kettering Cancer Center in New York City and The University of Texas MD Anderson Cancer Center in Houston, Texas, with Stephen Pastores, M.D., and Cristina Gutierrez, M.D., as Principal Investigators, respectively. The clinical trial is funded by the CRI Anna-Maria Kellen Clinical Accelerator, a program that supports and coordinates early-phase clinical trials of promising immuno-oncology combination therapies.

About the Cancer Research Institute
The Cancer Research Institute (CRI), established in 1953, is a top-rated U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 27 members of the National Academy of Sciences, CRI has invested $445 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org.

About the CRI Anna-Maria Kellen Clinical Accelerator
CRI’s clinical program, the Anna-Maria Kellen Clinical Accelerator, is a unique academia-nonprofit-industry collaboration model that serves as an “incubator” that delivers multi-center clinical trials for promising new immunotherapy combinations. CRI’s venture philanthropy fund supports clinical trials within this program, which fosters a collaborative environment that enables scientists to advance their most ambitious research ideas and accelerates studies that one group or company could not do alone. To learn more about the CRI Anna-Maria Kellen Clinical Accelerator, go to cancerresearch.org/clinical-accelerator.

About RevImmune
RevImmune is a privately held biotech company based in France, the U.S. and the U.K. RevImmune is in multiple Phase II trials with CYT107 for treatment of sepsis, certain infectious diseases, and certain cancers. Over 500 patients have been treated with CYT107 in RevImmune’s prior and current trials for multiple different viral diseases and sepsis. CYT107 showed an excellent safety profile and encouraging results in those trials. To learn more, go to revimmune.com.

Media Contacts:
For Cancer Research Institute: Brian Brewer, +1-212-688-7515 x242, bbrewer@cancerresearch.org
For RevImmune: Michel Morre, +33 6 03 35 70 60, mmorre@revimmune.com

 

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UCSF Study Explores Vaccination Immunity Questions – CBS San Francisco

UCSF Study Explores Vaccination Immunity Questions – CBS San Francisco

  • March 26, 2021

By Betty Yu and Molly McCrea

SAN FRANCISCO (KPIX) — With one in for Californians now at least partly vaccinated against COVID-19, questions are surfacing about the durability of the vaccine and how long will it protect the recipient from the virus.

READ MORE: Santa Clara County Health Officials Concerned Vaccine Supply Not Adequate as Eligibility Expands

Some people are also wondering what, if anything, can be done to boost their response to the vaccine.

UCSF scientists hope to find out and add to the growing body of scientific evidence. They are currently enrolling volunteers to help them better understand these important areas of inquiry.

To date, no one knows how long these COVID-19 vaccines will provide protection. Some experts believe the vaccine is good for at least six months and probably longer, but it is still too soon to tell.

Another added variable: the virus is changing, with new variants emerging.

“We are in a race against these variants,” noted Dr. David Kessler, who heads up the vaccine effort for the Biden Administration

Scientists know that not everybody responds equally well to the same vaccine.

“We’ve learned a lot about how vaccines work, but they don’t work the same for everyone,” said Dr. Aric Prather, a psychologist at UCSF and a specialist in insomnia.

Just how well these vaccines work, and for how long, may depend on the subject’s immune system and whether it has been compromised or weakened.

“It’s possible that those who are getting insufficient sleep or are excessively exposed to stress without the resilience factors are going to have a real decline in their antibody response,” noted Dr. Elissa Epel, a UCSF professor and Department of Psychology Vice Chair.

Dr. Prather and Dr. Epel are gathering data on the vaccine’s durability. Their goal is to identify what may impact an otherwise robust antibody response to the COVID-19 vaccine.

“We’re all so concerned right now with getting the vaccine and surviving this acute epidemic. But if we can’t maintain these antibodies, we’ll be looking at scenarios of flare ups, and needing more booster shots,” explained Dr. Epel.

The team is collecting blood from volunteers before and after their first COVID-19 vaccine for a study known as BOOST.

In the blood, scientists are not just measuring antibodies; they’re also looking at immune cells and searching for something called a telomere.

“They’re like the little protective tip at the end of a shoelace,” said UCSF’S Dr. Elizabeth Blackburn.

In 2009, Dr. Blackburn was one of the scientists who won the Nobel Prize in 2009 for the discovery of telomeres,

READ MORE: 3 Wounded, 1 Critically, Following Thursday Night Shooting in San Jose

Telomeres are clumps of DNA at the ends of chromosomes. They protect our chromosomes from damage. When it comes to telomeres, length matters.

“Telomere length has been related to how well the immune system is holding up,” explained Dr. Blackburn.

The longer the telomere, the better the protection.

“The longer they are, the more our immune cells are able to replicate themselves and robustly fight antigens,” said Dr. Epel.

As to what shortens telomeres: older age, lack of sleep, even chronic stress. Volunteers who participate in the study keep a diary and fill out periodic surveys about what’s going on with their lives.

“It was really very simple,” said Nancy, a volunteer for the BOOST study.

Nancy told KPIX she joined the study to help scientists better understand novel viruses, and to identify ways to bolster our immune response.

“You know the more we learn about how our bodies can produce antibodies after getting a vaccine, how well those antibodies are going to perform over time, I think it’s really important to find out,” she said.

As for the telomeres, you can lengthen them by sleeping more, eating a healthy diet, exercising and meditating to reduce stress.

“We know a lot about how to improve people’s level of stress,” explained Dr. Prather.

In the meantime, experts say everyone should get vaccinated when eligible.

Research shows the mindset of the person receiving the vaccine plays a role in the reaction. Studies indicate negative feelings can result in a weaker immune response to a flu shot.

As a way to improve response, it is suggested that before you receive a COVID-19 vaccine you get a good night’s sleep and walk in feeling positive. Volunteers are still welcome for the BOOST study, especially those who are 65 and older. There is a $300 compensation for those who are eligible to participate.

More information:

Learn about the study here.

Sign up for BOOST study here.

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Plant-based RG-I ingredient may support immune function, modulate the microbiota: Study

Plant-based RG-I ingredient may support immune function, modulate the microbiota: Study

  • March 25, 2021

Data published in Nutrients​ indicated that RG-I from bell pepper and carrot offered similar immune- and microbiota modulatory potential in vitro, while a proof-of-concept trial in humans showed that RG-I from bell pepper (bpRG-I) was well tolerated and enhanced innate immune responsiveness.

“RG-I enriched extracts prime innate immune responses and display a dual mode of action by exerting (1) an immunomodulatory effect on phagocytosis, a biomarker previously shown in some studies with ginseng-PS to be associated with protective effects against respiratory infections, and (2) a microbiota modulatory effect, with concomitant enhanced production of SCFA [short chain fatty acids],” ​wrote the researchers.

BeniCaros

The ingredients are being developed and commercialized by Netherlands-based NutriLeads. The privately held company was founded in 2012 and is and backed by investors including Icos Capital, Goeie Grutten, DSM Venturing, Oost NL, SHIFT Invest and Thuja Capital.

The company’s lead ingredient, BeniCaros, is extracted from carrot pomace, which itself is a side stream from carrot juice production. This ingredient is expected to be available in the US for the formulation of dietary supplements and functional foods in the second half of 2021.

Commenting on the publication and the expected impact of the findings, Ruud Albers, PhD, CEO of NutriLeads, said: “We are delighted to share these new data, demonstrating the immunomodulatory effects of plant-based RG-I, which have the potential to bring health benefits to us all. We are particularly pleased that we can successfully derive RG-I from sustainable and widely available sources.

Veto T-cells Boost Success of Stem Cell Transplant for SCD, Mouse Study Shows

Veto T-cells Boost Success of Stem Cell Transplant for SCD, Mouse Study Shows

  • March 23, 2021

Adding Cell Source’s special class of immune cell, Veto T-cells, to blood stem cells from an unrelated donor led to a successful transplant and to the production of normal red blood cells in a mouse model of sickle cell disease (SCD), the company announced.

The preclinical Cell Source-sponsored study supports the use of Veto T-cells to overcome the current challenges of blood stem cell transplants from unrelated donors, and highlights its curative potential for SCD.

“Our Veto Cell based protocol could overcome the lack of suitable donors, treatment toxicities, and graft-related challenges. This may have the potential to deliver a safe, effective, and durable curative treatment for patients with SCD,” Dennis Brown, chairman of Cell Source, said in a press release.

A Phase 1/2 trial (NCT03622788) is assessing the safety and efficacy of Veto T-cells at boosting the effectiveness of stem cell transplants in patients with blood-related diseases, including SCD. The trial, underway at the M.D. Anderson Cancer Center, Texas, aims to recruit 24 participants. More information about enrollment can be found here. The trial is expected to conclude by July.

The preclinical study, “Correction of murine sickle cell disease by allogeneic haematopoietic cell transplantation with anti-3rd party veto cells” was published in the journal Bone Marrow Transplantation.

An allogeneic hematopoietic stem cell transplant (Allo-HSCT) currently is the only available curative treatment for SCD. In this case, blood-forming stem cells are collected from a genetically matched donor, most often a sibling or an unrelated donor, and inserted into the patient to restore the production of normal red blood cells.

However, the scarcity of such donors is a major challenge. Moreover, Allo-HSCT can lead to graft-versus-host disease (GvHD), a condition in which immune cells, especially T-cells (cells that fight infections and cancer), from the donor are transplanted together with blood stem cells and view the recipient’s body as foreign, reacting against it. Conversely, the recipient’s immune system also may see the transplanted cells as a threat and react against them, leading to transplant rejection.

To reduce the chances of rejection, patients often are required to complete a conditioning regimen before receiving the transplant. The main goal of these conditioning regimens, which may include a combination of medications, chemotherapy, and/or radiation, is to suppress the patient’s immune system to the point it no longer can reject the transplanted cells.

While high-intensity conditioning regimens have been linked with increased toxicity, reduced-intensity conditioning regimens are typically safer, but less effective at preventing transplant rejection.

The risk of GvHD, in theory, also may be eliminated by resorting to T-cell-depleted HSCTs, meaning stem cell transplants that underwent a special treatment to remove most, if not all, donor T-cells. However, these transplants have been found more likely to fail.

One way to achieve a state of immune tolerance is to use donor T-cells with “veto” activity. This refers to the ability that certain T-cells, called Veto cells, have to halt or “veto” the harmful attacks of other T-cells. The Veto cells accompany the transplanted cells and work as a “decoy” by attracting the host’s attacking T-cells, which would reject the transplant and destroy them before they are able to do so.

According to Cell Source, Veto cells can increase the likelihood of transplant success, even when the HSCT comes from an unrelated donor who does not completely match the recipient, and allow for the use of a less-potent conditioning regimen that poses fewer risks to patients.

In this study, researchers at MD Anderson assessed the effectiveness of Cell Source’s proprietary Veto cells when given along with transplanted stem cells to a mouse model of SCD.

The animals received a T-cell-depleted HSCT from a mismatched donor, followed by a conditioning regimen with irradiation along with a short-term treatment with rapamycin. This previously was shown to facilitate the transplant process. A group of animals were given the donor-derived Veto cells, while another group remained untreated and served as controls.

First, researchers saw that animals treated with the Allo-HSCT plus the Veto cells — called chimeric mice — had a transplant success ranging from 77% to 94%, while no success was seen in control mice. This success percentage reflected the animals’ ability to produce donor-derived blood cells.

Chimeric animals continued showing signs of a successful transplant even after 318 days.

Moreover, chimeric animals showed normalization of key SCD parameters, including a normalization of the percentage of reticulocytes — immature red blood cells that usually are at increased levels in people with SCD — as well as in the concentration of white blood cells and hemoglobin.

Analysis of the animals’ organs showed that chimeric mice had significantly smaller spleens, while those of control animals remained enlarged.

Moreover, tissue analysis revealed that contrary to control mice, chimeric mice had no sickled red blood cells trapped in their spleen and kidneys, and their organs had a normal architecture.

Overall, the results of this preclinical study “demonstrate that our curative approach to SCD may potentially translate to safe and efficacious treatment in human patients,” said Brown.


Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

Total Posts: 50


Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.

Study results strengthen the case for using Regeneron’s antibody cocktail in high-risk Covid patients.

Study results strengthen the case for using Regeneron’s antibody cocktail in high-risk Covid patients.

  • March 23, 2021

A monoclonal antibody treatment developed by the drug maker Regeneron sharply cut the risk of hospitalization and death when given to high-risk Covid-19 patients in a large clinical trial, the company announced on Tuesday.

The results are the latest in a growing flurry of evidence that the infused drugs, meant to mimic the antibodies that the immune system generates naturally in fighting the coronavirus, can help infected patients avoid the worst outcomes if given early.

Regeneron’s treatment, a cocktail of two antibody drugs, was given last fall to President Donald J. Trump shortly after he got sick with Covid-19 and is now one of three such therapies available in the United States.

The new results come from a Phase 3 trial that enrolled more than 4,500 patients beginning in late September, around the time virus cases began to climb dangerously in the United States. The study found that patients who got the infused treatment within 10 days of developing symptoms or testing positive had a roughly 70 percent reduced risk of being hospitalized or dying compared with patients who were infused with a placebo.

“I think these are exciting data,” said Dr. Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital who was not involved in the study.

Even as vaccinations speed up, antibody treatments are expected to be helpful for high-risk people who still get sick for many months at least, and longer still if the virus can’t be wiped out. While there are signs that emerging virus variants may in some cases make antibodies less potent, Regeneron’s cocktail has not shown such vulnerability in laboratory tests.

In the new findings, Regeneron’s treatment worked equally well when given at half the dosing at which it was authorized. Regeneron said that it planned to request that the Food and Drug Administration allow the treatment to be given at that reduced strength.

Such a change would bring several advantages: While the cocktail is safe, getting it at a lower dose reduces the odds of side effects, such as an infusion reaction.

It would also allow Regeneron to increase the supply it can provide the United States. The company said that it had expected to supply the country with about 750,000 doses at the originally authorized higher strength by the end of June. If the lower strength is authorized, the company expects to provide about 1.25 million doses by then.

The antibody treatments from Regeneron and the drug maker Eli Lilly, which makes the other two such drugs authorized in the United States, were expected to be in high demand and to serve as a bridge in fighting the pandemic before vaccinations ramped up. Instead, they ended up sitting on refrigerator shelves in many places even during recent surges.

Many patients and their doctors did not know to ask for them or where to find them. Overwhelmed hospitals lacked the bandwidth to prioritize giving out the treatments. And some doctors were unconvinced by the relatively weak evidence available last fall supporting their use.

That picture is gradually shifting, thanks to improved logistics and more awareness. And more solid evidence, like the new data from Regeneron, also appears to be helping the drugs get used more widely. “As the data get stronger and stronger, I would expect that use will increase,” Dr. Gandhi said.

Children's immune response more effective against COVID-19 -- ScienceDaily

The findings of a new study may explain the microbiome-immunotherapy connection — ScienceDaily

  • March 22, 2021

Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system “sees” these bacteria and shown they can be harnessed to provoke an immune reaction against the tumor. The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research that the microbiome affects the success of immunotherapy.

Immunotherapy treatments of the past decade or so have dramatically improved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of the cases. Prof. Yardena Samuels of Weizmann’s Molecular Cell Biology Department studies molecular “signposts” — protein fragments, or peptides, on the cell surface — that mark cancer cells as foreign and may therefore serve as potential added targets for immunotherapy. In the new study, she and colleagues extended their search for new cancer signposts to those bacteria known to colonize tumors.

Using methods developed by departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial “guests” in cancer cells, Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system.

The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston, Texas; Prof Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Prof Eytan Ruppin of the National Cancer Institute, USA; Prof Arie Admon of the Technion — Israel Institute of Technology and other scientists.

The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes — complexes that are present on the membranes of all cells in our body and play a role in regulating the immune response. One of the HLA’s jobs is to sound an alarm about anything that’s foreign by “presenting” foreign peptides to the immune system so that immune T cells can “see” them. “Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner,” Kalaora says. “This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials.”

It’s unclear why cancer cells should perform a seemingly suicidal act of this sort: presenting bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.

This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.

Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. “Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation,” Nagler says.

In a series of continuing experiments, Samuels and colleagues incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically toward the bacterial peptides.

“Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy,” Samuels said. “They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs.”

Story Source:

Materials provided by Weizmann Institute of Science. Note: Content may be edited for style and length.

Freiburg researchers receive ERC funding to develop and test immunostimulatory drug candidates

New study shows how the immune system relates to cancer

  • March 22, 2021

Three University of Colorado Cancer Center researchers are part of a team that recently published a paper offering new insight into how the immune system relates to cancer. Quentin Vicens, PhD, Jeffrey Kieft, PhD, and Beat Vögeli, PhD, are authors on the paper, which looks at how an enzyme called ADAR1 operates in pathways associated with cancer.

“In a cell, ADAR1 edits native RNA — or self-RNA — so that the cell recognizes it as its own. It’s a key protection against autoimmune disorders,” Kieft says. “But if a virus infects, viral RNA isn’t edited by ADAR1, so the cell can recognize that and react. The cell knows it has foreign RNA, and it activates immune responses to fight off that infection.”

For their paper published last month in the journal Nature Communications, Kieft, Vögeli, Vicens, and the rest of the team — including Parker Nichols, a graduate student in the Structural Biology and Biochemistry program in the CU School of Medicine who works jointly in the Kieft and Vögeli labs — looked at where specifically the ADAR1 binds to RNA to perform the editing process. They already knew a domain of ADAR1 known as Z-alpha binds to a form of RNA called Z-RNA, but they found that Z-alpha ADAR1 can bind to other RNA forms as well.

The team asked, ‘How are all these locations in RNA being recognized by Z-alpha if they supposedly don’t form Z-RNA? One of the take-home messages is that other forms of RNA can bind to Z-alpha ADAR1 and can even partially form Z-RNA. That was a surprise because it shows that RNA can form this specific Z structure in places we didn’t recognize before.”


Jeffrey Kieft, PhD, Study Author, CU School of Medicine

The team is now proposing a model for how Z-alpha ADAR1 is able to bind to different types of RNA. It’s an important finding in cancer research because of the role of ADAR1 in cancer regulation. A normally functioning immune system oftentimes can detect cancerous cells as being dangerous and then eliminate them, but if there’s too much ADAR1 editing happening, a cell could be tamping down the immune response in an effort to protect itself.

“In a lot of cancers, there is upregulation of ADAR1; it is doing more than it should,” Kieft says. “The excess ADAR1 presumably is leading to more RNA editing than is normal. This is going to misregulate things, affecting specific regions of RNA or types of RNA.

The excess editing is going to throw off the normal immune response, but it probably has a lot of other affects in the cell as well. Cancer is a disease where gene regulation has gone awry, so if an important regulatory pathway like editing by ADAR has gone haywire, that can contribute to the cancer.”

Knowing all the targets of ADAR1 in a cell is also a step toward more effective therapies, Kieft says. If researchers understand the pathways, they may be able to find a way to disrupt the overactive editing process and boost the immune response. It’s a finding applicable to many other diseases as well — Vögeli says since the paper was published, the researchers have heard from other scientists around the country interested in ADAR1.

“We have gotten a lot of feedback on the paper,” he says. “There is a lot of interest in this field right now, and other people are interested in how they could use our structural information.”

Vögeli and Vicens are now organizing a meeting focused on ADAR1 function and putting together special issues of the journals Molecules and International Journal of Molecular Sciences.

Vicens says the research project also illustrates the importance of collaborative work and being open to new directions. “I basically brought a new project and direction to the Kieft lab when I joined,” Vicens says. “Both labs were open to supporting it intellectually and financially, and the resultant team effort enabled research that would not otherwise have been done.”

Source:

Journal reference:

Nichols, P. J., et al. (2021) Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions. Nature Communications. doi.org/10.1038/s41467-021-21039-0.

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