Tag: t cells

Antigens in Foods Suppress Gut Tumours by Activating Immune Cells

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Researchers led by Hiroshi Ohno at the RIKEN Center for Integrative medical sciences (IMS) in Japan have discovered that food antigens like milk proteins help keep tumours from growing in our guts, specifically the small intestines. Experiments revealed how these proteins trigger the intestinal immune system, allowing it to effectively stop the birth of new tumours. The study was published in the scientific journal Frontiers in Immunology.

Food antigens get a lot of negative press because they are the source of allergic reactions to foods such as peanuts, shellfish, bread, eggs, and milk. Even if not allergenic, these antigens, along with the many others found in plants and beans, are still considered foreign objects that need to be checked out by the immune system. Ohno and his team have previously reported that food antigens activate immune cells in the small intestines, but not the large intestines. At the same time, some immune cells activated by gut bacteria are known to suppress tumours in the gut. In the new study, the RIKEN IMS researchers bring these two lines of thought together and tested whether food antigens suppress tumours in the small intestines.

The team began with a mouse model with a mutated tumour-suppression gene. Like people with familial adenomatous polyposis, when this gene malfunctions, the mice develop tumours throughout the small and large intestines. The first experiment was fairly simple. They fed these mice normal food or antigen-free food and found that the ones that got normal food had fewer tumours in the small intestines, but the same amount in the large intestines.

Next, they added a common representative antigen called albumin – which can be found in meat and was not in the normal food – to the antigen-free diet, making sure that the total amount of the protein equalled the amount of protein in the normal diet. When the mice were given this diet, tumours in the small intestine were suppressed just as they has been with normal food. This means that tumour suppression was directly related to the presence of antigen, not the nutritional value of the food or any specific antigen.

Mice that got the plain antigen-free diet had many fewer T cells than those that got the normal food or the antigen-free food with milk protein. Further experiments revealed the biological process that makes this possible.

These findings have clinical implications. Similar to antigen-free diets, clinical elemental diets include simple amino acids, but not proteins. This reduces digestive work and can help people with severe gastrointestinal conditions, such as Crohn’s disease or irritable bowel syndrome. According to Ohno, “small intestinal tumours are much rarer than those in the colon, but the risk is higher in cases of familial adenomatous polyposis, and therefore the clinical use of elemental diets to treat inflammatory bowel disease or other gastrointestinal conditions in these patients should be considered very carefully.”

Elemental diets are sometimes adopted by people without severe gastrointestinal conditions or allergies as a healthy way to lose weight or reduce bloating and inflammation. The new findings suggest that this could be risky and emphasises that these kinds of diets should not be used without a doctor’s recommendation.

Source: RIKEN

Fever Drives Enhanced Activity and Mitochondrial Damage in Immune Cells

Photo by Kelly Sikkema on Unsplash

Fever temperatures accelerate immune cell metabolism, proliferation and activity, but in a particular subset of T cells, it also causes mitochondrial stress, DNA damage and cell death, Vanderbilt University Medical Center researchers have discovered. 

The findings, published in the journal Science Immunology, offer a mechanistic understanding for how cells respond to heat and could explain how chronic inflammation contributes to the development of cancer. 

The impact of fever temperatures on cells is a relatively understudied area, said Jeff Rathmell, PhD, Professor of Immunobiology and corresponding author of the new study. Most of the existing temperature-related research relates to agriculture and how extreme temperatures impact crops and livestock, he noted. It’s challenging to change the temperature of animal models without causing stress, and cells in the laboratory are generally cultured in incubators that are set at human body temperature: 37°C. 

“Standard body temperature is not actually the temperature for most inflammatory processes, but few have really gone to the trouble to see what happens when you change the temperature,” said Rathmell, who also directs the Vanderbilt Center for Immunobiology

Graduate student Darren Heintzman was interested in the impact of fevers for personal reasons: Before he joined the Rathmell lab, his father developed an autoimmune disease and had a constant fever for months on end. 

“I started thinking about what an increased set point temperature like that might do. It was intriguing,” Heintzman said. 

Heintzman cultured immune system T cells at 39°C. He found that heat increased helper T cell metabolism, proliferation and inflammatory effector activity and decreased regulatory T cell suppressive capacity. 

“If you think about a normal response to infection, it makes a lot of sense: You want effector (helper) T cells to be better at responding to the pathogen, and you want suppressor (regulatory) T cells to not suppress the immune response,” Heintzman said. 

But the researchers also made an unexpected discovery: that a certain subset of helper T cells, called Th1 cells, developed mitochondrial stress and DNA damage, and some of them died. The finding was confusing, the researchers said, because Th1 cells are involved in settings where there is often fever, like viral infections. Why would the cells that are needed to fight the infection die? 

The researchers discovered that only a portion of the Th1 cells die, and that the rest undergo an adaptation, change their mitochondria, and become more resistant to stress. 

“There’s a wave of stress, and some of the cells die, but the ones that adapt and survive are better – they proliferate more and make more cytokine (immune signaling molecules),” Rathmell said.

Heintzman was able to define the molecular events of the cell response to fever temperatures. He found that heat rapidly impaired electron transport chain complex 1 (ETC1), a mitochondrial protein complex that generates energy. ETC1 impairment set off signalling mechanisms that led to DNA damage and activation of the tumour suppressor protein p53, which aids DNA repair or triggers cell death to maintain genome integrity. Th1 cells were more sensitive to impaired ETC1 than other T cell subtypes.

 The researchers found Th1 cells with similar changes in sequencing databases for samples from patients with Crohn’s disease and rheumatoid arthritis, adding support to the molecular signaling pathway they defined. 

“We think this response is a fundamental way that cells can sense heat and respond to stress,” Rathmell said. “Temperature varies across tissues and changes all the time, and we don’t really know what it does. If temperature changes shift the way cells are forced to do metabolism because of ETC1, that’s going to have a big impact. This is fundamental textbook kind of stuff.” 

The findings suggest that heat can be mutagenic, when cells that respond with mitochondrial stress don’t properly repair the DNA damage or die. 

“Chronic inflammation with sustained periods of elevated tissue temperatures could explain how some cells become tumorigenic,” Heintzman said, noting that up to 25% of cancers are linked to chronic inflammation. 

“People ask me, ‘Is fever good or bad?’” Rathmell added. “The short answer is: A little bit of fever is good, but a lot of fever is bad. We already knew that, but now we have a mechanism for why it’s bad.” 

Source: Vanderbilt University Medical Center

Immune Cell Specialises its Roles in Different Tissues

Source: CC0

A newly published study in the scientific journal Science Immunology has investigating how MAIT cells (mucosa-associated invariant T cells) behave in different tissues. The Karolinska Institutet study shows that these immune cells, which play an important role in the body’s defence against microbes, exhibit different properties depending on the tissue they are in.

MAIT cells are a type of T cell that recognise by-products formed when microbes synthesise riboflavin. This makes them unique in the way they detect and fight infections. The researchers examined MAIT cells from blood, barrier tissues and lymphoid tissue samples from organ donors to understand how these cells function in different tissues.

Different MAIT cells in intestines and liver

“We found that MAIT cells in the intestines have a specialised immunoregulatory profile with high expression of the regulatory enzyme CD39, suggesting that they play a role in protecting the intestinal barrier,” says Johan Sandberg, Professor at the Center for Infectious Medicine (CIM), at the Department of Medicine, Huddinge, Karolinska Institutet.

“In the liver, on the other hand, MAIT cells predominantly exhibit high expression of the marker CD56 and an increased ability to fight microbes.”

The study also shows that the number of MAIT cells in the blood decreases with age but is preserved in the tissues. At the same time, tissue-adapted functions in the intestines and liver become increasingly evident with age.

“Our results highlight the functional heterogeneity of MAIT cells and their adaptation to different tissues.”

The results of the study add a new dimension to the understanding of the immune system and how different types of immune cells specialise to protect different tissues against infections.

“This gives us a better understanding of how this arm of the immune system works and can help us develop new treatments for infectious diseases,” says Johan Sandberg.

Source: Karolinska Institutet

Engineered T Cells aid the Recovery of Spinal Cord Injury

View of the spinal cord. Credit: Scientific Animations CC4.0

In a recent study published in Nature, researchers prevented T cells from causing the normal autoimmune damage that comes with spinal cord injury, sparing neurons and successfully aiding recovery in mouse models.

In spinal cord injury, the wound site attracts a whole host of peripheral immune cells, including T cells, which result in both beneficial and deleterious effects. Notably, antigen-presenting cells activate CD4+ T cells to release cytokines, ultimately leading to neuroinflammation and tissue destruction. This neuroinflammation is notably most pronounced during the acute phase of spinal cord injury. The problem is that these same T cells have a neuroprotective effect initially, only later developing autoimmunity and attacking the injury site.

Using single cell RNA sequencing, the researchers found that CD4+ T cell clones in mice showed antigen specificity towards self-peptides of myelin and neuronal proteins. Self-peptides have been implicated in a wide range of autoimmune conditions.

Using mRNA techniques, the researchers edited the T cell receptor, so that they shut off after a few days. In mouse models of spinal cord injury, they showed notable neuroprotective efficacy, partly as a result of modulating myeloid cells via interferon-γ.

Their findings provided insights into the mechanisms behind the neuroprotective function of injury-responsive T cells. This will help pave the way for the future development of T cell therapies for central nervous system injuries, and perhaps treatments for neurodegenerative diseases such as Alzheimer’s.

US Fast-Tracks a Promising New Therapy for Metastatic Prostate Cancer

Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

The US Food and Drug Administration (FDA) has granted Fast Track designation for SYNC-T SV-102 therapy for the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC). SV-102 is part of Syncromune Inc.’s SYNC-T platform, an in situ personalised therapy that uses a combination multi-target approach to cancer treatment, aiming to improve outcomes and quality of life for patients.

The Fast Track designation was granted based on the potential of SYNC-T SV-102 therapy to address the significant unmet need in treating patients with mCRPC. This advanced form of prostate cancer affects over 40 000 men in the US alone and is associated with a very poor prognosis. The Fast Track process is designed to facilitate the development and expedite the review of therapies that treat serious conditions and fulfil an unmet medical need, with the goal of getting important new treatments to patients sooner. Fast Track designation provides Syncromune with several key benefits, including more frequent FDA interactions, eligibility for accelerated approval, and priority review.

“The Fast-Track designation for SYNC-T SV-102 therapy signifies another step forward in bringing our potentially groundbreaking therapy to patients who need it most,” said Eamonn Hobbs, Chief Executive Officer and co-founder of Syncromune. “This accomplishment builds upon the foundation of positive Phase 1 clinical data and recent IND clearance.”

Syncromune’s lead candidate, SYNC-T SV-102, is a platform therapy that combines an in situ vaccine via partial oncolysis of a tumour followed by intratumoural infusion of the SV-102 fixed-dose multi-target biologic drug into the lysed tumour. This combination is designed to provide both immune stimulation and block immune suppression to activate and proliferate T cells to elicit a systemic anti-tumour response. Interim data from a Phase 1 study of SV-102 in males with mCRPC demonstrated an overall response rate of 85% with a favourable safety profile and tolerability. The Fast-Track designation comes on the heels of clearance of the company’s investigational new drug (IND) application, with studies expected to begin in the US this year.

Charles Link, M.D., Executive Chairman of Syncromune added, “We believe that Fast-Track designation for SYNC-T SV-102 will significantly aid our development goals for this therapy for men with difficult to treat prostate cancer. We look forward to initiating trials at multiple US sites later this year to expand our efforts to develop the SYNC-T SV-102 Therapy.”

Source: Syncromune

How Glucocorticoids Reprogram Immune Cells to Slow them Down

Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

Cortisone and other related glucocorticoids are extremely effective at curbing excessive immune reactions. But previously, astonishingly little was known about how they exactly do that. A team of researchers have now explored the molecular mechanism of action in greater detail. As the researchers report in the journal Nature, glucocorticoids reprogram the metabolism of immune cells, activating the body’s natural “brakes” on inflammation. These findings lay the groundwork for development of anti-inflammatory agents with fewer and less severe side effects.

The glucocorticoid cortisone is naturally present in the body as the stress hormone cortisol, which is released to improve the body’s responses to stress. Cortisol intervenes in sugar and fat metabolism and affects other parameters, including blood pressure and respiratory and heart rate. At higher doses, it also inhibits immune system activity, making it it useful for medical purposes. Due to their excellent efficacy, synthetic glucocorticoid derivates that inhibit inflammation even more strongly are used to treat a wide range of immune-mediated inflammatory diseases.

Glucocorticoids affect not only genes, but also cellular energy sources

Glucocorticoid-based medications come with side effects, especially at higher doses and when administered for longer periods. These side effects are related to the other effects of the body’s own cortisol, and include hypertension, osteoporosis, diabetes, and weight gain. With the aim of developing anti-inflammatory agents with fewer and less severe side effects, a team of researchers from from Charité – Universitätsmedizin Berlin, Uniklinikum Erlangen and Ulm University has now conducted a closer study of how the immunosuppressive effects of glucocorticoids exactly works.

Lead researcher Prof Gerhard Krönke, director of the Department of Rheumatology and Clinical Immunology at Charité, explains: “It was previously known that glucocorticoids activate a number of genes in different cells of the body. But through this mechanism, they mainly activate the resources present in the body. This does not adequately explains its strong immunosuppressive effect. In our study, we have now been able to show that glucocorticoids affect more than just the gene expression in immune cells. It also affects the cell´s powerhouses, the mitochondria. And that this effect on cell metabolism is in turn crucial to the anti-inflammatory effects exerted by glucocorticoids.”

Swords to plowshares

For the study, the research team focused on macrophages, a type of immune cell responsible for eliminating intruders such as viruses and bacteria. These cells can also play a role in the emergence of immune-mediated inflammatory diseases. In a mouse model, the researchers studied how these immune cells responded to inflammatory stimuli in a laboratory setting and what effects additional administration of a glucocorticoid had. The researchers observed that in addition to its effect on gene expression, glucocorticoids had a major effect in reversing changes in the cell metabolism that had been initiated by the inflammatory stimuli.

“When macrophages are put into ‘fight’ mode, they redirect their cellular energy into arming for a fight. Instead of supplying energy, their mitochondria produce the components needed to fight intruders,” Krönke says, describing the processes involved. “Glucocorticoids reverse the process, switching the ‘fight’ mode back off and turning swords into plowshares, so to speak. A tiny molecule called itaconate plays an especially important role in this.”

Itaconate mediates anti-inflammatory effect of glucocorticoids

Itaconate is an anti-inflammatory substance that the body naturally produces inside its mitochondria. Macrophages produce it early on when they are activated so that the inflammatory reaction will subside after a certain period. Generation of this natural immune “brake,” however, requires sufficient fuel. When the cell´s powerhouses are arming up for a fight, that is no longer the case, so itaconate production dwindles to a halt after a while. With normal, short-term inflammation, this timing is effective because the immune response has also subsided in the meantime.

“With a persistent inflammatory stimulus, the drop-off in itaconate production is an issue because there is then no immune ‘brake’ even though the immune system is still running on all cylinders, eventually contributing to chronic inflammation,” explains Dr Jean-Philippe Auger, a scientist at the Department of Medicine 3 – Rheumatology and Immunology at Uniklinikum Erlangen and the first author of the study. “This is where glucocorticoids intervenes. By reprogramming the mitochondrial function, they ramp up the formation of itaconate in the macrophages, restoring its anti-inflammatory effect.”

The search for new active substances

Using animal models for asthma and rheumatoid arthritis, the researchers showed how much the anti-inflammatory effect of glucocorticoids depends on itaconate. Glucocorticoids had no effect in animals unable to produce itaconate. So, if itaconate mediates the immunosuppressant effect of cortisone, what about administering itaconate directly, instead of glucocorticoids?

“Unfortunately, itaconate isn’t a particularly good candidate as an anti-inflammatory drug, because it’s unstable, and due to its high reactivity, it could cause side effects if administered systemically,” Krönke explains. “Aside from that, we assume the processes in humans to be a bit more complex than those in mice. So our plan is to look for new synthetic compounds that are just as effective as glucocorticoids at reprogramming the mitochondrial metabolism inside immune cells, but have fewer and less severe side effects.”

Source: Charité – Universitätsmedizin Berlin

New Trial Highlights Incremental Progress Towards a Cure for HIV-1

Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).

Antiretroviral therapies (ART) stop HIV replication in its tracks, allowing people with HIV to live relatively normal lives. However, despite these treatments, some HIV still lingers inside cells in a dormant state known as “latency.” If ART is discontinued, HIV will awaken from its dormant state, begin to replicate, and cause acquired immunodeficiency syndrome (AIDS). To create a cure, researchers have been attempting to drive HIV out of latency and target it for destruction.

A new clinical trial led by Cynthia Gay, MD, MPH, associate professor of infectious diseases, David Margolis, MD, the Sarah Kenan Distinguished Professor of Medicine, Microbiology & Immunology, and Epidemiology, and other clinicians and researchers at the UNC School of Medicine suggests that a combination of the drug vorinostat and immunotherapy can coax HIV-infected cells out of latency and attack them.

The immunotherapy was provided by a team led by Catherine Bollard, MD, at the George Washington University, who took white blood cells from the study participants and expanded them in the laboratory, augmenting the cells’ ability to attack HIV-infected cells, before re-infusion at UNC.

Their results, published in the Journal of Infectious Diseases, showed a small dent on the latent reservoir, demonstrating that there is more work to be done in the field.

“We did show that this approach can reduce the reservoir, but the reductions were not nearly large enough, and statistically speaking were what we call a “trend” but not highly statistically significant,” said David Margolis, MD, director of the HIV Cure Center and senior author on the paper. “We need to create better approaches to flush out the virus and attack it when it comes out. We need to keep chipping away at the reservoir until there’s nothing there.”

DNA inside cell nuclei is kept in a tightly packed space by chromosomes, which act as highly organised storage facilities. When you unfurl a chromosome, you’ll find loop-de-loop-like fibres called chromatin. If you keep unfurling, you’ll see long strands of DNA wrapped around scaffold proteins known as histones, like beads on a string. Finally, when the unfurling is complete, you will see the iconic DNA double helix.

Vorinostat works by inhibiting a lock-like enzyme called histone deacetylase. By stopping this mechanism, tiny doors within the chromatin fibres unlock and open up, effectively “waking up” latent HIV from its slumber and making it vulnerable to an immune system attack. As a result, a tiny blip of HIV expression shows up on very sensitive molecular assays.

But the effects of vorinostat are short lived, only lasting a day per dose. For this reason, Margolis and other researchers are trying to find safe and effective ways to administer the drug and keep the chromatin channels open for longer periods of time.

For the study, six participants were given multiple doses of vorinostat. Researchers then extracted immune cells from the participants and expanded the cells that knew how to attack HIV-infected cells.

This immunotherapy method, which has been successful against other viruses such as Epstein-Barr virus and cytomegalovirus, involves giving participants back their expanded immune cells in the hopes that these cells will further multiply in number and launch an all-out attack on the newly exposed HIV-infected cells.

However, in the first part of this study, only one of the six participants saw a drop in their HIV reservoir levels. To test whether the result was simply random or something more, researchers gave three participants their usual dose of vorinostat, but introduced five times the amount of engineered immune cells. All three of the participants had a slight decline in their reservoirs.

But, statistically speaking, the results were not large enough to be definitive.

“This is not the result we wanted, but it is research that needed to be done,” said Margolis. “We are working on improving both latency reversal and clearance of infected cells, and we hope to do more studies as soon as we can, using newer and better approaches.”

Many of the participants in the study have been working with Margolis’s research team for years, sacrificing their own time and blood for research efforts. Their long-term partnership and commitment have been essential for data collection. The data, which follows the size of the viral reservoir in these people over years prior to this study, makes the small changes found more compelling.

“People living with HIV come in a couple of times a year, and we measure residual traces of virus in their blood cells, which doesn’t have any immediate benefit to them,” said Margolis. “It’s a very altruistic action and we couldn’t make any progress without their help.”

Source: University of North Carolina Health Care

Understanding How T Cells Target Tuberculosis will Enhance Vaccines and Therapies

Tuberculosis bacteria. Credit: CDC

La Jolla Institute for Immunology (LJI) is working to guide the development of new tuberculosis vaccines and drug therapies. Now a team of LJI scientists has uncovered important clues to how human T cells combat Mycobacterium tuberculosis, the bacterium that causes TB. Their findings were published recently in Nature Communications.

“This research gives us a better understanding of T cell responses to different stages in tuberculosis infection and helps us figure out is there are additional diagnostic targets, vaccine targets, or drug candidates to help people with the disease,” says LJI Research Assistant Professor Cecilia Lindestam Arlehamn, PhD, who led the new research in collaboration with LJI Professors Bjoern Peters, PhD, and Alessandro Sette, Dr.Biol.Sci.

The urgent need for TB research

According to the World Health Organization, more than 1.3 million people died of TB in 2022, making it the second-leading infectious cause-of-death after COVID. “TB is a huge problem in many countries,” says Lindestam Arlehamn.

Currently, a vaccine called bacille Calmette-Guerin (BCG) protects against some severe cases of TB. Unfortunately, BCG doesn’t consistently prevent cases of pulmonary TB, which can also be deadly.

Although there are drug treatments for TB, more and more cases around the world have proven drug resistant.

To help stop TB, Lindestam Arlehamn and her colleagues are learning from T cells. Instead of targeting an entire pathogen, T cells look for specific markers, called peptides sequences, that belong to the pathogen.

When a T cell recognises a certain part of a pathogen’s peptide sequence, that area is termed an “epitope.”

Uncovering T cell epitopes gives scientists vital information on how vaccines and drug treatments might take aim at the same epitopes to stop a pathogen.

T cells take aim at a range of TB epitopes

For the new study, the researchers worked with samples from patients who were mid-treatment for active TB. These samples came from study participants in Peru, Sri Lanka, and Moldova.

By looking at T cells in patients from three different continents, the researchers hoped to capture a wide diversity of genetics and environmental factors that can affect immune system activity.

In their analysis, the LJI team uncovered 137 unique T cell epitopes. They found that 16% of these epitopes were targeted by T cells found in two or more patients. The immune system appeared to be working hard to zoom in on these epitopes.

Going forward, Lindestam Arlehamn’s laboratory will investigate which of these epitopes may be promising targets for future TB vaccines and drug therapies.

A step toward better diagnostics

The new study is also a step toward catching TB cases before they turn deadly.

Because Mycobacterium tuberculosis is an airborne bacteria, a person can be exposed without ever realizing it. Once exposed, many people go months or years without any symptoms.

This inactive, or “latent,” TB can turn into active TB if a person’s immune system weakens, for example, during pregnancy or due to an infection such as HIV.

For the new study, the researchers also compared samples from active TB patients with samples from healthy individuals.

The scientists uncovered key differences in T cell reactivity between the two groups.

“For the first time, we could distinguish people with active TB versus those that have been exposed to TB – or unexposed individuals,” says Lindestam Arlehamn.

Lindestam Arlehamn says it may be possible to develop diagnostics that detect this tell-tale T cell reactivity that marks a person’s shift from latent to active TB. “Can we use this peptide pool to look for high-risk individuals and try and follow them over time?” she says.

Source: La Jolla Institute for Immunology

New T Cell ‘Rescue’ Therapy Promising for ARDS

Credit: Scientific Animations CC4.0

Promising trial results indicate that a new type of cell therapy could improve the prognosis of those who are critically ill with acute respiratory distress syndrome (ARDS) resulting from severe COVID.

Published in the journal Nature Communications, Professor Justin Stebbing of Anglia Ruskin University (ARU) is the joint senior author of the new study investigating the use of agenT-797, MiNK Therapeutic’s allogeneic, unmodified invariant natural killer T (iNKT) cell therapy.

The iNKT cell therapy has the effect of rescuing exhausted T cells and prompting an anti-inflammatory cytokine response, potentially activating anti-viral immunity to help these patients fight infection as well as to reduce severe, pathogenic inflammation of the lung.

The new research was carried out at three medical centres and found that agenT-797, which is also under investigation in cancer trials, could be manufactured rapidly, had a tolerable safety profile, and appeared to have a positive effect on mortality among critically unwell Covid-19 ARDS patients receiving intensive care.

The exploratory trial included 20 mechanically ventilated patients with severe ARDS secondary to Covid-19. Of the 20 patients in the trial, 14 survived (70%) at 30 days (compared to a control group of 10%), and there was an 80% lower occurrence of bacterial pneumonia amongst those who received the highest dosage of agenT-797, compared to those who received fewer cells.

Twenty-one patients were treated overall (the main trial, plus one under compassionate use), which included five who were also receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), known as ‘the most aggressive salvage therapy’ for critically ill patients with ARDS.

In VV-ECMO, deoxygenated blood is pumped through a membrane lung and returned to the body via a cannula. This trial is believed to be the first immune cell therapy of any type to be used in critically unwell patients undergoing VV-ECMO.

Survival of the VV-ECMO cohort was 80% after 30 and 90 days, and 60% after 120 days. This compares favourably to overall survival of 51% for patients with Covid-19 who were treated with just VV-ECMO at the same institution, during the same timeframe.

Joint senior author Justin Stebbing, Professor of Biomedical Sciences at Anglia Ruskin University (ARU) in Cambridge, England, said: “During this small, exploratory study we observed that MiNK’s iNKT cell treatment, which is also being advanced for people with cancer, triggered an anti-inflammatory response in ARDS patients.

“Despite a poor prognosis, critically ill patients treated with this therapy showed favourable mortality rates and those treated at the highest dose also had reduced rates of pneumonia, underscoring the potential application of iNKT cells, and agenT-797 in particular, in treating viral diseases and infections more broadly.

Source: Anglia Ruskin University

New Therapy Eliminates ‘Problematic’ T Cells in Skin Autoimmune Diseases

Photo: CC0

In a groundbreaking study published in Science, researchers discovered distinct mechanisms controlling different types of immune cells, and found that, by precisely targeting these mechanisms, they could selectively eliminate ‘problematic cells’ and reshape the skin’s immune landscape.

The skin is packed with specialised immune cells that protect against infections and cancer and promote healing. These cells, called tissue-resident T cells or TRM cells, stay in place to fight infections and cancerous cells in the skin.

However, when not controlled properly, some of these skin TRM cells can contribute to autoimmune diseases, such as psoriasis and vitiligo.

Researchers, led by University of Melbourne’s Professor Laura Mackay, a Laboratory Head and Immunology Theme Leader at the Peter Doherty Institute of Infection and Immunity (Doherty Institute), found a way to redress this imbalance.

University of Melbourne’s Dr Simone Park, an Honorary Research Fellow and former Postdoctoral Fellow in the Mackay Lab at the Doherty Institute, and lead first author of the study, said that this research is the first to describe the unique elements that control various types of skin TRM cells in animal models, offering precise targets for potential treatment strategies.

“Specialised immune cells in our skin are diverse: many are critical to prevent infection and cancer, but others play a big role in mediating autoimmunity,” said Dr Park.

“We discovered key differences in how distinct types of skin T cells are regulated, allowing us to precisely edit the skin’s immune landscape in a targeted way.”

University of Melbourne’s Dr Susan Christo, Senior Research Officer in the Mackay Lab at the Doherty Institute and co-first author of the study, explained how these discoveries could advance efforts to treat skin disease.

“Most autoimmune therapies treat the symptoms of the disease rather than addressing the cause. Conventional treatments for skin disorders often impact all immune cells indiscriminately, meaning that we could also be wiping out our protective T cells,” said Dr Christo.

“Until now, we didn’t know how to pick apart ‘bad’ T cells in the skin from the ‘good’ protective ones. Through this research, we discovered new molecules that allow us to selectively remove disease-causing T cells in the skin.”

The research team harnessed this new knowledge to eliminate ‘problematic’ cells that can drive autoimmune disorders, while preserving the ‘good’ ones that are essential to maintain protective immunity.

University of Melbourne’s Professor Laura Mackay, senior author of the study, explained that these findings could pave the way for more precise and long-lasting therapies for skin disease.

“Skin conditions like psoriasis and vitiligo are difficult to treat long-term. The T cells driving disease are hard to remove, so patients often need life-long treatment. Our approach has the potential to revolutionise the way we treat these skin disorders, significantly improving outcomes for people dealing with challenging skin conditions,” said Professor Mackay.

With the study demonstrating successful removal of specific skin T cells in animal models, further research is necessary to validate the efficacy of these strategies in human subjects.

Dr Park hopes the study will inspire the development of new treatments for skin disease.

“These discoveries bring us one step closer to developing new drugs that durably prevent autoimmune skin disorders without compromising immune protection,” said Dr Park.

Source: The Peter Doherty Institute for Infection and Immunity