Category Archives: Immunology

Boosting vaccines for the elderly with ‘hyperactivators’ – Boston Children’s Answers – Boston Children’s Discoveries

As we age our immune systems start to flag, leaving us more susceptible to cancer and infections and less responsive to vaccines and cancer immunotherapies.

Going to the heart of the problem, Jonathan Kagan, PhD, a researcher in immunology at Boston Childrens Hospital, has identified a way to rejuvenate the elderly immune system. His teams findings, published this month in the journal Cell, could lead to stronger vaccine adjuvants to help fight cancer and infectious diseases in older people.

For our immune systems to effectively defend against cancer or infections, certain key things need to happen. Dendritic cells, also known as antigen-presenting cells, are first responders: They take a snapshot of the invader, travel to the lymph nodes, and show T cells the snapshot. T cells then rally: CD4 T cells activate other types of immune cells, while CD8 T cells fight invaders directly.

However, with age, dendritic cells lose their ability to migrate, so T cells never receive their intelligence. When dendritic cells cant migrate, its like having a house invader and having no phone to call the cops, Kagan says.

On top of that, older people also make fewer T cells, in particular fewer killer CD8 T cells.

Using an elderly mouse model of cancer, Kagans team turned to hyperactivators, naturally occurring fatty molecules found in inflamed tissue that stimulate immune responses. Could some of these responses be useful for immunization?

Weve investigated hyperactivators for quite a while, Kagan says. We began isolating them in 2014 or 2015 and asked how they behave when added to dendritic cells.

When the team gave hyperactivators to elderly mice, dendritic cells did indeed migrate to the lymph nodes at more than 250 times the rate seen with commercially available vaccine adjuvants like alum and LPS.

Although CD8 T cells were largely depleted in elderly mice, the hyperactivated dendritic cells somewhat surprisingly were able to induce CD4 T cells, which acquired long-lasting killer functions and were able to eradicate implanted tumors. In contrast, checkpoint inhibitors a common type of cancer immunotherapy did not protect elderly mice.

Kagan is further investigating how the hyperactivators mobilize dendritic cells and broader immune responses. In this study, the compounds increased numbers of a receptor called CCR7 on dendritic cells. CCR7 senses chemokines produced in the lymph nodes, Kagan explains. Without the receptor, dendritic cells cant see the signals to migrate.

Boston Childrens has filed patent applications on Kagans work and licensed them to Corner Therapeutics, co-founded by Kagan in 2019. (Kagan currently serves as an advisor and board member.) The company is focused on developing proprietary versions of the hyperactivators that can be used clinically.

In the lab, Kagan now wants to demonstrate that hyperactivators are effective in more human-like cancer models, as well as in infectious diseases starting with influenza. His ultimate goal is to create cancer vaccines as well as next-generation infectious disease vaccines that mobilize dendritic cells.

The last 10 years have been the age of T cell-targeting therapies, he says. But because T cells are diminishing with age, these therapies lose their usefulness as people get older. We need to diversify the targets of immunotherapies.

Learn more about Kagans research

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Boosting vaccines for the elderly with 'hyperactivators' - Boston Children's Answers - Boston Children's Discoveries

Immunologists Want You to Know These Dust Mite Allergy Facts – Yahoo Lifestyle UK

Because microscopic dust mites are invisible to the naked eye, they seem like an elusive storybook creature that may or may not loom among our homes. But their presence quickly becomes known when theyre responsible for an unexplained allergic reactionwhich brings us to the question: Do dust mites bite? Below, an immunologist and allergist explain everything you need to know.

Meet the Experts: Sharlene Llanes, M.D., an allergist and immunologist with AllerVie Health, Loxahatchee and James Faix, M.D., medical director of immunology at Quest Diagnostics.

Dust mites are microscopic, insect-like creatures that are found in homes, explains Sharlene Llanes, M.D., an allergist and immunologist with AllerVie Health, Loxahatchee. James Faix, M.D., medical director of immunology at Quest Diagnostics adds that they are found in house dust corralled in soft surfaces like rugs, sofas, bedding, and clothing where they live on a diet of shed human skinkeyword being shed, meaning they do not bite to feed. They dont bite, but they feed off the dead skin of humans and pets, says Dr. Llanes. With that being said, contact with dust mites can cause uncomfortable allergic reactions.

A dust mite allergy might take on the appearance of insect bites, or a skin rash, says Dr. Faix. It also can manifest as asthma or allergy-like upper respiratory symptoms. Heres a comprehensive list of signs to watch for, per Dr. Faix and Dr. Llanes:

Treatment of a dust mite allergy depends on the symptomsallergic rhinitis, or your typical seasonal allergy qualms, can be addressed with over-the-counter antihistamines and decongestants, Dr. Faix says. Patients with moderate symptoms may require intranasal corticosteroids, and patients with severe symptoms who do not respond to these measures may be candidates for immunotherapy, he adds, which gradually exposes a person to dust mites to get their immune system accustomed to them.

Asthma-like symptoms need treated on an individual basis by a primary care doctor or immunologist, says Dr. Faix, but may include steroids and/or an albuterol inhaler.

With all of that being said, both Dr. Faix and Dr. Llanes say that the most effective treatment of a dust mite allergy is eliminating the source of the allergenmeaning getting rid of carpets, drapes, stuffed toys, and other soft surfaces, generally cleaning and decluttering, and installing an air purifier with a HEPA filter.

In short: Cleanliness is key, says Dr. Faix. That means vacuuming at least weekly and washing bedding and other upholstery in hot water regularly, he recommends. You can also minimize places for them to dwell by opting for hardwood floors and leather furniture. HEPA air purifiers and dehumidifiers can also help keep the air in your home dry and clean. To learn more, check out our guide on how to get rid of dust mites.

You can prevent excess dust mites by maintaining cleanliness, minimizing soft surfaces and textiles like stuffed toys and carpet, and using an air purifier with a HEPA filter, Dr. Llanes says. She also suggests keeping household humidity at 50% because dust mites thrive in warm, humid environments. Even if you check all of those boxes, though, Dr. Llanes stresses that its nearly impossible to completely eliminate dust mites from the home. They are everywhere, she says. As long as there is a human in a home, dust mites are there to stay.

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How Ragon Institute’s new building aids its mission Harvard Gazette – Harvard Gazette

On its 15th anniversary, the Ragon Institute celebrates the opening of a 300,000-square-foot building to house its engineers, scientists, and doctors. The Cambridge-based Ragon a collaboration between Massachusetts General Hospital, MIT, and Harvard enables cross-disciplinary biomedical research aimed at solving global health problems. We spoke with Ragon Director Bruce Walker about the Institutes next steps.

This interview was edited for clarity and length.

The Ragon Institute was founded to bring about collaboration between scientists, doctors, and engineers. How does the new building facilitate this?

Traditionally, these scientific disciplines have been siloed. So one objective is to bring these different disciplines together, but unless theyre interacting you havent accomplished much. What weve done is to create an environment where the incentive is to leave your office and go to common spaces that we refer to as collaboration spaces where you have those chance encounters, where the scientists are visible. The Institute is built so that you can see people. Its got a very large central atrium and catwalks on each level and a spiral staircase, so you know who else is in the building. In my experience, those random encounters are where innovation and creativity are spawned.

You can work really hard to create something through the application of science and engineering, but if you cant deliver it to people you havent accomplished much.

Do you see any new disciplines or technologies being added to this collaboration?

Were all studying how the immune system functions and how it malfunctions. Whether youre a physicist or a computational biologist or an immunologist, were all working toward a common goal of understanding those processes. The immune system is beyond the capacity of the human brain to understand that whole complex system, but its not beyond the ability with AI and machine learning. In the new building there will be multiple spaces for computational biologists, AI, and machine learning.

As you celebrate the Ragons 15th anniversary, do you see its focus changing?

We have three major programmatic areas now going forward. We have just the beginning of an understanding of how the immune system works, but we know that that the immune system is in every nook and cranny in our bodies and keeping us healthy. In fact, its eliminating cancerous cells as they arise. The more we can understand about it, the better we can come up with therapies. So trying to understand the physiology of the immune system is one focus.

Immune engineering is another, and the third is patient-centered immunology. You can work really hard to create something through the application of science and engineering, but if you cant deliver it to people you havent accomplished much. One of the things that we have in the new building is a clinical center. Well be able to do patient follow-up right in the institute.

What new challenges will the Institute take on?

A major challenge looking forward is the family of neurodegenerative diseases like Parkinsons and Alzheimers. Theres a lot of evidence suggesting that those are inflammatory in nature, in other words, mediated in some way or modulated in some way by the immune system. And so neuroimmunology is one of the areas that were specifically trying to extend into. We started out 15 years ago as an HIV institute, we rapidly expanded as Ebola and then Zika came along, and COVID-19, influenza, malaria, and in addition to that, autoimmunity and cancer. Its all under the umbrella of how the immune system functions and malfunctions.

What has the partnership between Harvard, MIT, and Massachusetts General Hospital made possible?

It has enabled us to implement our strategy, which was to bring together scientists from different disciplines and give them the flexibility to take innovative ideas forward with flexible funding. Traditional funding sources are loath to fund things if they havent been shown to already work, and our view is that if we arent failing in some projects, were not pushing the envelope hard enough. The flexible funding is really critical because it enables us to take an idea and immediately sprint with it, taking high-risk, high-impact ideas forward.

For years when I was working at Mass General, I would have conversations with different people outside of the HIV field and wed talk about, Wow, wouldnt it be great to apply your skills to this HIV problem? And it never went anywhere because we never had funding. Were enabling those connections to happen by catalyzing them with flexible funding.

How do you see this partnership growing?

We are MGH, MIT, and Harvard, but we welcome people from all the other affiliated hospitals. We collaborate with UMass and Tufts and Boston University.

Our educational mission is not just local, it extends out to other places in the world, particularly South Africa, which has the greatest burden of TB and HIV infection in the world. We partner closely with two research institutes there, and our goal is to transfer the knowledge and technologies that were developing to the African continent and to help in training the next generation of African scientists.

Were in the process of establishing new collaborations in South America and others in Africa. And we are establishing a formal collaboration with a new institute in Australia. Again, we really want to take down the walls.

What difference will this new facility make?

The expanded facilities allow us to cover more dimensions of immunology, recruit more faculty, and provide an expanded number of better-equipped labs to support the scientists. It was built for collaboration, which is the reason that the Ragon Institute was built: to bring together scientists and engineers and medical doctors from multiple disciplines and use their creativity and knowledge in a pooled way to solve some of the biggest global health problems of our generation and future generations.

The Institute also has a childcare center, to support young faculty with families, and educational spaces to teach the next generation of scientists and engineers and medical doctors. We actually overbuilt things, so its got a very large biosafety Level 3 facility, which will service people in this incredible square mile of scientific innovation thats unmatched anywhere in the world.

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How Ragon Institute's new building aids its mission Harvard Gazette - Harvard Gazette

Insights into CRS and NPs: Visual and Bibliometric Analysis – Physician’s Weekly

The following is a summary of Visual and bibliometric analysis of chronic rhinosinusitis and nasal polyps, published in the May 2024 issue of Allergy & Immunology by Liu, et al.

Chronic rhinosinusitis (CRS) is characterized by persistent nasal and sinus passages inflammation and an imbalance in the sinus microbiome. Nasal polyps (NPs) are a significant manifestation of CRS, contributing to various clinical symptoms. For a study, researchers sought to perform a bibliometric and visual analysis of research articles on CRS and NPs published from 2003 to 2022 to provide insights into the current state of research and identify future directions.

The Web of Science database searched relevant articles published between 2003 and 2022. The bibliometric analysis was conducted using VOSviewer and the Bibliometrix R package.

The analysis included 3,907 publications. The United States was the most significant contributor to global research, followed by China. Northwestern University had the highest number of publications. C. Bachert was identified as the most prolific author, with R. P. Schleimer and R. J. Schlosser also notable. The most frequently co-cited authors were C. Bachert, W. J. Fokkens, and P. Gevaert. The International Forum of Allergy & Rhinology had the most publications, while the Journal of Allergy and Clinical Immunology was the most cited. Current research hotspots included Covid-19, biologics, and type 2 inflammation.

The United States and Northwestern University were identified as leading contributors to CRS and NP research. C. Bachert emerged as the most influential researcher. The International Forum of Allergy & Rhinology and the Journal of Allergy and Clinical Immunology were prominent journals in the field. Emerging research areas included Covid-19, biologics, and type 2 inflammation.

Reference: jaci-global.org/article/S2772-8293(24)00007-9/fulltext

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Insights into CRS and NPs: Visual and Bibliometric Analysis - Physician's Weekly

Biogen joins immunology wave with $1.15 billion acquisition of HI-Bio – STAT

Biogen is joining the industrys fervor over immune and inflammatory disease drug development with a new acquisition.

The Cambridge, Mass., drugmaker announced Wednesday that it will acquire Human Immunology Biosciences, or HI-Bio, for $1.15 billion and up to $650 million in additional payments if certain milestones are met.

HI-Bio, which is based in San Francisco, is developing therapies for immune-mediated diseases like primary membranous nephropathy and IgA nephropathy, both of which impact kidney function. The startups lead drug, felzartamab, is a monoclonal antibody that selectively depletes CD38+ and natural killer cells in the hopes of alleviating the diseases effects. It has already completed Phase 2 studies.

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Biogen joins immunology wave with $1.15 billion acquisition of HI-Bio - STAT

Biogen Buys Desired Growth In Immunology With $1.15bn Hi-Bio Deal – Scrip

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Biogen Boosts Immunology Portfolio with $1.8 Billion Acquisition of HI-Bio – BioPharm International

Biogens acquisition of HI-Bio includes lead investigational mAb, felzartamab, under development for treating a range of immune-mediated diseases.

Biogen announced on May 22, 2024 that it has entered into a definitive agreement to acquire Human Immunology Biosciences (HI-Bio), a privately-held US-based clinical-stage biotechnology company focused on targeted therapies for severe immune-mediated diseases (IMDs). Under the agreement, Biogen will pay $1.15 billion upfront and up to $650 million in potential milestone payments. The transaction is expected to close in the third quarter of 2024, pending necessary regulatory approvals and customary closing conditions.

With the acquisition, Biogen gains felzartamab, HI-Bios lead asset. Felzartamab is a fully human anti-CD38 monoclonal antibody (mAb) that has been shown to selectively deplete CD38+ cells in clinical studies. This selective depletion includes plasma cells and natural killer (NK) cells. This action may allow for additional applications that improve clinical outcomes in a broad range of immune-mediated diseases, Biogen stated in a company press release.

We believe this late-stage asset, which has demonstrated impact on key biomarkers and clinical endpoints in three renal diseases with serious unmet needs, is a strategic addition to the Biogen portfolio as we continue to augment our pipeline and build on our expertise in immunology, said Priya Singhal, MD, head of Development at Biogen, in the press release. We look forward to welcoming HI-Bio employees into Biogen and, together, working to advance potential therapies for patients with rare immune diseases with high unmet need.

FDA has granted felzartamab breakthrough therapy designation and orphan drug designation for development in treating primary membranous nephropathy (PMN). The mAb has also received orphan drug designation for treating antibody-mediated rejection (AMR) in kidney transplant recipients. Felzartamab has completed Phase II studies in PMN and AMR and remains in ongoing Phase II studies in immunoglobulin A nephropathy (IgAN). HI-Bio plans to advance the mAb to Phase III studies in each indication; the company is presenting two abstracts at the European Renal Association Congress in Stockholm, which is occurring May 2326, 2024. HI-Bios presentation includes complete Phase II data from the AMR study in kidney transplant patients and interim data from the Phase II IgAN study, according to the press release. Studies have also generated clinical data for felzartamab in the AMR, PMN, and IgAN indications.

With its deep development and commercialization capabilities, Biogen is in a position to accelerate the development of new medicines, including felzartamab, for patients with severe immune-mediated diseases, said Travis Murdoch, MD, chief executive officer of HI-Bio, in the release. We are excited to combine the HI-Bio teams expertise with Biogens global footprint.

In addition to the felzartamab lead program, HI-Bios pipeline consists of izastobart/HIB210, an anti-C5aR1 antibody currently in a Phase I trial. This candidate has the potential for continued development in a range of complement-mediated diseases. HI-Bio also has discovery-stage mast cell programs with potential application in a range of immune-mediated diseases.

The treatment of IMDs has largely benefitted from the evolution of targeted biologic therapies. Targeted biologics have demonstrated efficacy, speed of onset, and tolerability. Whats more, research efforts have shown that clinically unrelated immune-mediated inflammatory conditions can share similar immune dysregulation. This discovery has since led to a shift in way IMDs and other inflammatory disorders are managed (1).

1. Kuek, A.; Hazleman, B. L.; Ostr A. J. Immune-Mediated Inflammatory Diseases (IMIDs) and Biologic Therapy: A Medical Revolution. Postgrad Med J. 2007, 83 (978), 251260. DOI: 10.1136/pgmj.2006.052688

Source: Biogen

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Biogen Boosts Immunology Portfolio with $1.8 Billion Acquisition of HI-Bio - BioPharm International