Category Archives: Immunology

Absci, The Kennedy Institute for immunotherapies development – Pharmaceutical Technology

Absci has collaborated with the University of Oxfords Kennedy Institute of Rheumatology to expedite the development of AI-driven immunotherapies.

The collaboration will use the integrated drug creation platform of Absci and the clinical immunology datasets from the Kennedy Institute to identify antibodies to immune-mediated inflammatory diseases and autoimmune conditions with unprecedented speed.

Absci will utilise the generative AI models with genomics datasets from the Kennedy Institute to identify new antibodies from patients with immune responses to inflammatory bowel disease (IBD), ulcerative colitis and Crohns disease.

The company will then reassemble the antigen-antibody pairs, using its reverse immunology approach, as starting points for the development of drugs.

Absci founder and CEO Sean McClain stated: The Kennedy Institutes vast, high-quality biorepository data expand Abscis strategic research and development portfolio and aim to unlock major advances for a range of immune-mediated conditions that millions suffer from.

Together with our established data partnerships with St. Johns Cancer Institute and Aster Insights, this partnership gives Absci a robust data pipeline that enables our AI platform across a wide range of therapeutic areas as we build our internal therapeutic pipeline.

The companys integrated drug creation platform combines data, AI and wet-lab capabilities for screening several cells per week.

This allows the platform to move from AI-designed antibodies to lab-validated candidates in as little as six weeks.

The Kennedy Institute clinical research director Christopher Buckley stated: Abscis reverse immunology approach promises to turn clinical data into pharmaceutical drugs.

We are excited about the potential for generative AI to accelerate the discovery of promising drug candidates and better understand their potential efficacy and safety profiles.

This partnership will help accelerate our findings in the clinic into new immunotherapies for patients.

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Absci, The Kennedy Institute for immunotherapies development - Pharmaceutical Technology

Customizing T Cell-Based Immunotherapies in a ‘SNAP’ – UPMC

5/9/2023

PITTSBURGH University of Pittsburgh researchers have developed a universal receptor system that allows T cells to recognize any cell surface target, enabling highly customizable CAR T cell and other immunotherapies for treating cancer and other diseases. The discovery could extend into solid tumors and give more patients access to the game-changing results CAR T cell therapy has produced in certain blood cancers.

Described in a Nature Communications study published today, the new approach involves engineering T cells with receptors bearing a universal SNAPtag" that fuses with antibodies targeting different proteins. By tweaking the type or dose of these antibodies, treatments could be tailored for optimal immune responses.

The researchers showed that their SNAP approach works in two important receptors: CAR receptors, a synthetic T cell receptor that coordinates a suite of immune responses, and SynNotch, a synthetic receptor that can be programmed to activate just about any gene. With the addition of SNAP, the possibilities for customized therapies become almost endless.

We showed for the first time that we can make a universal SynNotch receptor. This SNAP-SynNotch system is super programmable because you can have both designer input and designer gene output, said senior author Jason Lohmueller, Ph.D., assistant professor of surgery and immunology in the division of surgical oncology at the Pitt School of Medicine and investigator at UPMC Hillman Cancer Center. Our hope is that we can use this approach to make cell therapies and deliver genes for cancer, autoimmune disorders, organ transplantation tolerance and more.

CAR T cell immunotherapy involves engineering a patients own cells so that the T cell receptor recognizes a specific protein on cancer cells before infusing them back into the patient.

One of the big problems with CAR T therapy is that youre targeting just one protein, explained Lohmueller. If the tumor evolves to lose that protein or downregulate it, you need to re-engineer the T cells a second time, which is a highly involved and expensive process.

To overcome this problem, Lohmueller, first author Elisa Ruffo, Ph.D., postdoctoral associate at Pitt, Alexander Deiters, Ph.D., professor of chemistry at Pitt and their colleagues developed universal SNAP-CAR T cells by adding a SNAPtag enzyme to the CAR receptor. These cells are administered along with cancer-targeting antibodies that are labeled with a molecule called benzylguanine.

Via a bio-orthogonal chemistry a type of reaction that occurs in living systems without interfering with natural processes the SNAPtag reacts with benzylguanine, fusing the antibody to the receptor. Adding different antibodies, at the same time or one after another, allows the receptor to recognize different tumor features.

Whats unique about our approach is how the T cell interacts with the antibody. Its not just binding, but fusing via covalent attachment the strongest form of chemical bond, explained Lohmueller. This type of bio-orthogonal approach has been shown to work in animals for imaging purposes, but were among the first to use it therapeutically, so were really pushing the boundaries of covalent technology.

An advantage of this tight bond means that activation of the receptor can be achieved with lower doses of antibody, said Lohmueller. Using mathematical modeling, graduate student Adam Butchy and Natasa Miskov-Zivanov, Ph.D., assistant professor of electrical and computer engineering at Pitts Swanson School of Engineering, showed that it may also be possible to get activity from weaker interactions between antibodies and tumor cells, giving greater flexibility to the types of cancer proteins that can be targeted.

The covalent bond was also the secret ingredient for creating SNAP-SynNotch cells. When a SynNotch receptor is activated, mechanical pulling forces stretch the receptor to expose part of the protein, which is then cut to release a transcription factor that travels to the cells nucleus to turn on expression of a chosen gene.

We found that we needed the strength of a covalent bond to tolerate that pulling force, explained Lohmueller. If we just had binding between receptor and antibody, the receptor would come apart and we wouldnt get signaling.

The researchers showed that their universal SNAP-CAR and SNAP-SynNotch receptors could be activated in response to different targets by adding the corresponding antibodies. SNAP-CAR T cells were also able to simultaneously target multiple proteins on different types of cells, suggesting that they could help avoid cancer relapse due to variation in tumor targets or loss of those targets.

In a mouse model of cancer, treatment with SNAP-CAR T cells shrunk tumors and greatly prolonged survival, an important proof-of-concept that sets the stage to test this approach in clinical trials in partnership with Coeptis Therapeutics, which has licensed the SNAP-CAR technology from Pitt.

Other authors on the study were Yaniv Tivon, Victor So, Michael Kvorjak, Avani Parikh, M.S., Eric L. Adams, M.D., and Olivera J. Finn, Ph.D., all of Pitt or UPMC.

This work was supported by the National Institutes of Health (R01 GM142007, R35 CA210039, R21 AI130815, 1S10OD011925-01 and P3 0CA047904), the Defense Advanced Research Projects Agency (W911NF-17-1-0135), the Italian Foundation for Cancer Research (22321), and the Michael G Wells Prize.

PHOTO DETAILS: (click image for high-res version)

CREDIT: Jason LohmuellerCAPTION: Jason Lohmueller, Ph.D., assistant professor of surgery and immunology in the division of surgical oncology at the Pitt School of Medicine and investigator at UPMC Hillman Cancer Center

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Customizing T Cell-Based Immunotherapies in a 'SNAP' - UPMC

Understanding Lupus: an interview with the Garvan Institute – News-Medical.Net

To commemorate World Lupus Day, we spoke to Elissa Deenick, co-lead of the Precision Immunology Program at the Garvan Institute, about the current state of lupus understanding and what needs to happen to make lupus visible.

My name is Elissa Deenick, Im a lab head and co-lead of the Precision Immunology Program at the Garvan Institute of Medical Research in Sydney, Australia, and a Scientia A/Prof at UNSW Sydney. I have 20 years of experience studying the signals that control immune cells. My research asks how we can ensure these cells make a protective immune response while avoiding harmful responses such as autoimmunity (where the immune system attacks our own bodies) and allergy. I do this by studying patients with rare genetic diseases that disrupt the immune system and applying what we learn there to understand how the immune system goes wrong in other diseases like lupus.

The exact pathophysiology of lupus and what drives it is very complicated and there are likely many factors involved. We do know that in lupus, B cells, which usually make antibodies that protect us from infection, end up making antibodies against normal parts of the body like DNA. These antibodies then bind to their targets like DNA, forming what is called immune complexes. These can build up in different parts of the body like the kidney, joints or the skin where they induce inflammation and cause the damage that we know is associated with lupus.

The incidence of lupus seems to be increasing and thats true of many autoimmune diseases so lupus is part of that trend. That increase is probably, in part, an increase in awareness and diagnosis, but theres almost certainly a real increase in incidence there as well. However, it is not clear why these diseases are increasing thats something we really need more research to understand.

Weve discovered different ways in which the immune system can become dysregulated and cause inappropriate production of antibodies.

For example, poor clearance of dead or dying cells (which means there are dead bits of cells in places they shouldnt be, containing things like DNA that can activate B cells), dysregulation of B cells, and inappropriate production of cytokines such as interferons.

But despite the fact that our understanding of lupus has increased, we still dont have a cure for lupus and patients are largely dependent on immunosuppressive drugs that can put them at risk of side effects such as infections.

One of the biggest issues in lupus is that its almost certainly not one disease, but instead a cluster of diseases with similar symptoms but completely different drivers of disease in different people. And of course, if the underlying cause of disease is different from patient to patient, then the most effective treatment is also likely going to differ too. This heterogeneity amongst patients probably partly explains why many clinical trials of new drugs have failed in the past: you may have 10% of people in the lupus population who may respond well to that drug, but thats going to be obscured by the other 90% of people who respond poorly because thats the wrong drug for them. The focus for research then needs to be on ways to identify the driver of disease in each patient so we can match the drug to the disease.

One of the ways that Im approaching that question is by studying rare patients who have what are called inborn errors of immunity. These are caused by rare genetic variants in key genes that are important for the immune system. These genetic variants disrupt the function of those pathways and make the immune system go wrong. And in some cases, part of the way they make it go wrong is that B cells produce these pathogenic antibodies that cause autoimmunity and lupus. The significance of this for us is that it identifies pathways that can be drivers of disease. So what were doing is studying those pathways and then seeing if they might also be drivers in other patients with lupus (even if they dont have the genetic variant).

Image Credit: adike/Shutterstock.com

Another question were interested in is the infections in lupus patients. People with lupus have a higher risk of severe infections, which can require time in hospital to get them under control. The problem is, though, that were not good at predicting which people with lupus are at the highest risk of infection. Were trying to work out ways of predicting who is at greatest risk and whether thats because of the immunosuppressive drugs theyre on or whether its something thats intrinsic to the dysregulation of their immune system.

Recent advances in single-cell sequencing techniques, such as single-cell RNA sequencing, have enabled us to analyse immune cell populations in patients at an unprecedented level of detail. These technologies are illuminating how immune responses differ between people and vary under different conditions, such as in lupus patients or in individuals with COVID-19 infections. With new insight into these granular differences, we can achieve a much deeper understanding of how the immune system functions in both health and disease. This has enabled a deeper dive into human immunology, including lupus pathology.

I think there is increasing awareness about lupus and that may be in part from celebrities coming out but also I think the COVID-19 pandemic has driven a greater understanding of the immune system in general. The general public is now much more familiar with talking about B cells and T cells and antibodies, so when people ask me about my work theres already a much greater level of understanding of these concepts. I think that helps with understanding and awareness of immune-mediated disease as well.

Image Credit: Rito Succeed/Shutterstock.com

Again, I think the idea that lupus is one disease with one solution is quite commonplace, unfortunately. The reality is that the experience of lupus is very different from person to person and not all lupus can be treated in the same way.

I think we need to keep hearing stories directly from the people who are affected by lupus how it affects their lives and health. Many people still have misconceptions about what lupus is and how serious and life-altering it can be, but sharing real stories is a powerful way to raise awareness and build empathy.

A/Prof Elissa Deenick is head of the Lymphocyte Signalling and Activation Lab and co-leads the Precision Immunology Program at the Garvan Institute of Medical Research. She is a Scientia A/Prof at the Faculty of Medicine and Health, UNSW Sydney.

A/Prof Deenick undertook her PhD with Dr Phil Hodgkin at the Centenary Institute/University of Sydney. Following her PhD she moved to Canada to take up a postdoctoral position in the lab of Dr Pam Ohashi at the University of Toronto, looking at the signalling pathways controlling T cell activation and tolerance.

She returned to Sydney to work at the Garvan Institute of Medical Research, where she continues to uncover the signals controlling lymphocyte activation and differentiation and how this is controlled to ensure protection against infection while avoiding harmful immune responses like allergy and autoimmunity.

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Danielle graduated with a 2:1 in Biological Sciences with Professional Training Year from Cardiff University. During her Professional Training Year, Danielle worked with registered charity the Frozen Ark Project, creating and promoting various forms of content within their brand guidelines. Danielle has a great appreciation and passion for science communication and enjoys reading non-fiction and fiction in her spare time. Her other interests include doing yoga, collecting vinyl, and visiting museums.

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Understanding Lupus: an interview with the Garvan Institute - News-Medical.Net

Professor Laura Mackay wins LEO Foundation Award in Region … – The Peter Doherty Institute for Infection and Immunity

Professor Laura Mackay, Laboratory Head and Immunology Theme Leader at the Doherty Institute, and National Health and Media Research Council (NHMRC) Leadership Fellow at the University of Melbourne, has been awarded the LEO Foundation Award in Region Asia-Pacific for her contributions to our understanding of T cells and their relevance for immunology memory.

The prestigious honour, which was announced at the International Societies for Investigative Dermatology (ISID) in Japan earlier this week, aims to highlight outstanding young researchers and scientists from around the world whose work represents an extraordinary contribution to skin research.

Professor Mackay praised the support of the LEO Foundation for early- and mid-career researchers, like herself, and said she was honoured to receive the recognition.

The LEO Foundations work to highlight young skin researchers will greatly support our teams pursuit to understand the role of memory T cells in the skin, Professor Mackay said.

It is an honour to be recognised for this award among the talented pool of researchers across the Asia-Pacific region and to be afforded the opportunity to champion skin immunology research.

Based in Denmark, the LEO Foundation 's philanthropic awards and grants aim to support the best international research in skin diseases.

Three times a year, three outstanding scientists from the Americas, Europe, Middle East and Africa (EMEA) and Asia-Pacific receive a LEO Foundation Award to support their promising research in skin health. The Awards are granted in open competition with all award applications being evaluated by an independent and international global review panel.

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Professor Laura Mackay wins LEO Foundation Award in Region ... - The Peter Doherty Institute for Infection and Immunity

Trinity’s Prof Ed Lavelle recognised by ISI for vaccine research – SiliconRepublic.com

Lavelle primarily focuses on developing injectable and mucosal vaccines for infectious diseases, along with therapeutic vaccines for cancer.

Prof Ed Lavelle of Trinity College Dublin has been recognised by the Irish Society for Immunology (ISI) for his major contributions to immunology research and education.

He has received the ISIs Annual Award, which is given to outstanding Irish immunologists that push forward our understanding of immunology and health improvement.

Lavelle works in Trinitys School of Biochemistry and Immunology, with his research primarily focused on developing injectable and mucosal vaccines for infectious diseases.

He also leads a research group that is developing therapeutic vaccines for cancer and investigating vaccine strategies that promote immunogenic cell death, with the goal of enhancing protective immunity.

Lavelle was the president of the ISI from 2012 until 2020, during which time he organised multiple conferences, chaired session and acted as a peer reviewer for immunology journals. He has also supervised 21 PhD students to completion.

In 2019, Lavelle received nearly 96,000 from the Science Foundation Ireland (SFI) Technology Innovation Development Award (TIDA) programme. This SFI programme provides capital and training in entrepreneurship skills to researchers that seek to commercialise their lifes work.

Last year, Lavelle was a recipient of Trinitys Innovation Awards, receiving one of the years inventors awards, along with Dr Marco Ruffini of Trinitys School of Computer Science and Statistics.

Lavelle will present a public lecture at 7pm tonight (9 May) in the Tercentenary Hall in Trinitys Biomedical Sciences Institute. This lecture will get to the core of how vaccines work and is available for anyone to attend.

This is a golden era for vaccine research and we hope that our work on vaccine adjuvants can contribute to further advances, particularly for cancer vaccination where there is a desperate need for novel and more effective approaches, Lavelle said.

Last month, Trinity awarded its 2023 Dawson prize in Genetics toDr Katalin Karik, the Hungarian-born scientist whose research into mRNA vaccines helped create life-saving vaccines against Covid-19.

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Allison Institute announces appointment of inaugural members – EurekAlert

HOUSTON The James P. Allison Institute at The University of Texas MD Anderson Cancer Center today announced the appointment of its first members, James P. Allison, Ph.D., Padmanee Sharma, M.D., Ph.D., Jennifer Wargo, M.D., Sangeeta Goswami, M.D., Ph.D., and Kenneth Hu, Ph.D. In addition, Garry Nolan, Ph.D., will join the Allison Institute as an adjunct member.

These members include pioneering researchers who have made notable contributions to science as well as rising stars on the path toward important breakthroughs. This group will bring diverse expertise in immunobiology to lead groundbreaking research that will deepen our understanding of the immune system and bring the benefits of immunotherapy to all patients.

We are proud to be joined by these stellar scientists, and we are confident that together we will set the tone for the exceptional research we aim to support at the Allison Institute, said Allison, director of the Allison Institute and regental chair of Immunology at MDAnderson. Our collective expertise in areas that now will include immune-microbiome interactions, epigenetic mechanisms, and novel methods for spatial transcriptomics and proteomics fits well with our priority research areas, and we look forward to collaboratively advancing the field.

The Allison Institute was launched to drive breakthroughs that will integrate immunobiology across disciplines. Building on a deep commitment to discovery science, Allison Institute members will incorporate laboratory and clinical insights to develop novel and synergetic therapies that enable cures for more patients.

MD Anderson is committed to integrating exceptional science across disciplines to deliver meaningful advances for patients, said Giulio Draetta, M.D., Ph.D., chief scientific officer at MDAnderson. The Allison Institute and its members are a testament to that approach, and I look forward to the collective discoveries to come from these researchers working seamlessly together and across the institution.

New members bring diverse expertise, include rising stars and established scientists

Institute members are selected based on alignment with research priority areas and are approved by the Allison Institute director and scientific advisory board.

Membership levels include:

Core, associate and assistant members are provided with seven years of research support aligned with their membership level. In addition, they have joint appointments in MDAnderson academic departments, enabling them to collaborate seamlessly with clinicians and scientists across the institution. Adjunct members are recruited to collaborate with the Allison Institute and provided resources to support specific projects aligned with the institutes research goals.

Our members represent the top minds from around the world, with diverse skill sets and backgrounds, and we are pleased to expand understanding through our work at the Allison Institute, said Sharma, director of scientific programs for the Allison Institute and professor ofGenitourinary Medical OncologyandImmunology at MDAnderson. Through our unique research model, we aim to unleash their individual brilliance in a collaborative and inclusive environment and to train the next generation of immunotherapy leaders.

In addition to their leadership roles, Allison and Sharma are appointed as core members and will continue to lead impactful research focused on optimizing the use of immunotherapy to improve patient outcomes.

James P. Allison, Ph.D., is recognized internationally for his foundational discoveries in T cell biology that launched the field of cancer immunotherapy. For his contributions, he was awarded the 2018 Nobel Prize in Physiology or Medicine. His most notable discoveries include determining the T cell receptor structure and recognizing that CD28 is the major costimulatory molecule that allows full activation of nave T cells and prevents anergy in T cell clones. His lab resolved a major controversy by demonstrating that CTLA-4 inhibits T cell activation by opposing CD28-mediated costimulation and that blockade of CTLA-4 could enhance T cell responses, leading to tumor rejection in animal models. He proposed and validated that blocking immune checkpoints, such as CTLA-4, can be a powerful cancer treatment strategy. These seminal findings established the field of immune checkpoint blockade therapy for cancer and led to the development of ipilimumab, the first FDA-approved immune checkpoint inhibitor. Allisons current work seeks to improve current immune checkpoint blockade therapies and to identify new targets that will unleash the immune system to eradicate cancer.

Padmanee Sharma, M.D., Ph.D., is an internationally renowned physician scientist who pioneered the first neoadjuvant clinical trial with immune checkpoint therapy in 2006, establishing safety and clinical responses in order to advance immunotherapy toward earlier disease stages. Her work also provided the first clinical data demonstrating that bladder tumors can respond to immune checkpoint therapy. Sharma performs extensive studies on patients tumor samples collected from neoadjuvant trials to define human immune responses within the tumor microenvironment and to identify mechanisms of response and resistance to checkpoint inhibitors. She has identified mechanisms of response to immune checkpoint therapy, including ICOS+ T cells, tertiary lymphoid structures and ARID1A mutations in combination with CXCL13 overexpression. Her work has also identified mechanisms of resistance, including VISTA+ myeloid cells, increased EZH2 expression in T cells, and loss of interferon signaling in tumor cells. These data enable Sharma to lead innovative pre-clinical and clinical studies testing new combination immunotherapies and biomarkers. As a core member, she will work closely with other researchers to build scientific teams that bridge multiple areas of expertise to design novel treatment strategies.

Jennifer Wargo, M.D., who joins the Allison Institute as a core member, is professor ofSurgical OncologyandGenomic Medicineand director ofMDAnderson'sPlatform for Innovative Microbiome and Translational Research (PRIME-TR). A world-renowned physician scientist, Wargo pioneered a new understanding of how the gut microbiome influences responses to immunotherapy and other cancer treatments. Through this research, she and her team have determined how microbiome changes can positively impact immunotherapy responses, leading to an ongoing dietary intervention trial in melanoma. As a core member, Wargo will continue to lead innovative research on the impact of the gut and tumor microbiome on cancer and immunotherapy responses. She is committed to advancing the understanding and treatment of disease through science, and she is deeply invested in working broadly with investigators to find better ways to treat, intercept and prevent cancer.

Sangeeta Goswami, M.D., Ph.D., joining as an assistant member, is assistant professor of Genitourinary Medical Oncology and Immunology at MD Anderson. A gifted physician scientist, Goswami both cares for patients with bladder and kidney cancers and conducts exceptional discovery and translational research that integrates the fields of epigenetics and immunology. She is leading pioneering studies focused on identifying epigenetic pathways that regulate differentiation and function of immune cell subsets. Goswamis current research focuses on uncovering key epigenetic factors involved in primary and adaptive resistance to immunotherapy, especially myeloid cell-mediated suppressive pathways. This will guide strategies to target these factors and overcome immunotherapy resistance in tumors with high levels of myeloid cells, such as glioblastoma. She aims to design rational therapeutic combinations of epigenetic modulators and immune checkpoint inhibitors in a tumor-specific manner.

Kenneth Hu, Ph.D., joins the Allison Institute as an assistant member. Recruited from the University of California San Francisco through a Cancer Prevention and Research Institute of Texas (CPRIT) award, Hu will join MD Anderson as assistant professor of Immunology. His research interests are founded in developing novel tools to push the boundaries of measurable cell states and interactions. As a graduate student, he adapted atomic force microscopy to study single-cell generated forces and mechanical properties. While a postdoctoral researcher, he developed ZipSeq, a novel technique using light-based uncaging of nucleotides to barcode cells of interest and map single-cell sequencing data back to defined regions in a tissue. His research at MD Anderson will focus on broadening the applications of this technique to study spatial tumor heterogeneity and its role in dictating responses to immunotherapy.

Garry Nolan, Ph.D., who joins the Allison Institute as an adjunct member, is the Rachford and Carlota A. Harris Professor in the department of Pathology at Stanford University School of Medicine. His research interests include hematopoiesis, cancer and leukemia, autoimmunity and inflammation, and computational approaches for network and systems immunology. His efforts are aimed at enabling a deeper understanding of normal immune function as well as detailed substructures of leukemias and solid cancers and their interactions with the immune system. Nolans lab developed a novel approach for single cell analysis advance using a mass spectrometry-flow cytometry hybrid device, called CyTOF. His collaboration with the Allison Institute will focus on a second technology developed in his lab, CODEX (CO-Detection by indEXing). This innovative in situ imaging approach allows for the simultaneous visualization of dozens of proteins and/or RNA targets in a single tumor sample. Joining his expertise with patient samples collected by MD Andersons immunotherapy platform will help elucidate the interactions between tumor and cells in the immune microenvironment for both primary tumors and metastases.

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Allison Institute announces appointment of inaugural members - EurekAlert

Study sheds light on how the immune system protects the body – EurekAlert

First study of humans with a rare immunodeficiency reveals how the immune system protects the body against pathogens known to cause serious diseases, such as tuberculosis and COVID-19. The research involving McGill University, paves the way for new therapies to treat autoimmune diseases, chronic inflammatory diseases, and new approaches to vaccine development.

The immune system responds differently to various types of pathogens, like bacteria, parasites, and viruses. However, scientists are still trying to uncover how this complex network functions together and the processes that can go wrong with immunodeficiencies.

The immune system plays a vital role in protecting the body from harmful germs that make people ill. Its made up of a complex network of organs, cells, and proteins like IRF1 or regulatory factor 1, which is key in the regulation of an early immune response to pathogens, says co-author of the study David Langlais, an Assistant Professor in the Departments of Human Genetics and Microbiology and Immunology at McGill University.

A better understanding of these specific processes will help us pinpoint the cause of defective immune responses, and perhaps even allow to boost an appropriate immune response to better combat illness, adds Langlais who is also a Principal Investigator at the Victor Phillip Dahdaleh Institute of Genomic Medicine.

Previous studies on mice that were IRF1 deficient have shown that the animals were highly susceptible to many viruses. In studying the first human patients with IRF1 deficiency ever identified, the researchers found that while the patients were highly susceptible to some bacterial infections, surprisingly they can defend themselves normally against viruses, including COVID-19.

This study provides new insight into the mechanisms underlying the human immune responses to mycobacteria, which includes pathogens known to cause tuberculosis, versus differences in the immune response to viruses. Unlike in mice, we show that in humans, the activity of IRF1 is not essential to anti-viral immunity, says co-author Jrg Fritz, who is also an Associate Professor in the Department of Microbiology and Immunology.

Based on our findings, it could be possible to think of therapeutic avenues to block or activate the action of IRF1 and control the type and intensity of immune responses. Our findings shed light on our understanding of the specificity and selectivity of our immune responses towards different pathogens, says co-author Philippe Gros, a Professor in the Department of Biochemistry and Principal Investigator at the Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill.

Human IRF1 governs macrophagic IFN-g immunity to mycobacteria by Jrmie Rosain et al. was published in Cell.

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Study sheds light on how the immune system protects the body - EurekAlert

Werewolf Therapeutics Reports First Quarter 2023 Financial Results … – BioSpace

WATERTOWN, Mass., May 11, 2023 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the Company or Werewolf) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the bodys immune system for the treatment of cancer, today provided a business update and reported financial results for the first quarter ended March 31, 2023.

In the first quarter, Werewolf has focused on execution by progressing our INDUKINE pipeline and enrolling ongoing first-in-human clinical trials for our lead programs, WTX-124 and WTX-330. In addition, preclinical data presented at AACR and published in Cancer Immunology Research continues to demonstrate the robustness of our PREDATOR platform showing that Werewolfs conditional activation technology results in potent anti-tumor activity alongside an improved therapeutic index, said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. Looking ahead, in the fourth quarter we plan to share initial safety, tolerability, and preliminary efficacy data from our Phase 1/1b clinical trial of WTX-124 in solid tumor types.

Finally, wed like to express our deep appreciation to Reid Leonard, Ph.D., Werewolfs Chief Operating Officer, who is retiring effective June 30, 2023, after a long and successful career in the biopharmaceutical industry. Reid is a founding member of the Werewolf Executive Team and has been instrumental in leading and advancing all aspects of organizational operations. We have benefited greatly from Reids significant expertise, and the strong team he has built and business process he has established will ensure continued operational excellence going forward. We wish Reid the very best in his retirement.

Recent Highlights and Upcoming Milestones

WTX-124:a systemically delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE molecule being developed as monotherapy and in combination with checkpoint inhibitor therapy in multiple solid tumor types.

WTX-330:a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in refractory and/or immunologically unresponsive tumors.

Early-Stage Pipeline:

Financial Results for the First Quarter of 2023:

About Werewolf Therapeutics:Werewolf Therapeutics, Inc. is an innovative biopharmaceutical company pioneering the development of therapeutics engineered to stimulate the bodys immune system for the treatment of cancer. We are leveraging our proprietary PREDATOR platform to design conditionally activated molecules that stimulate both adaptive and innate immunity with the goal of addressing the limitations of conventional proinflammatory immune therapies. Our INDUKINE molecules are intended to remain inactive in peripheral tissue yet activate selectively in the tumor microenvironment. Our most advanced clinical stage product candidates, WTX-124 and WTX-330, are systemically delivered, conditionally activated Interleukin-2 (IL-2), and Interleukin-12 (IL-12) INDUKINE molecules, respectively, for the treatment of solid tumors. We expect to advance WTX-124 in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor and WTX-330 in multiple tumor types or Non-Hodgkin Lymphoma as a single agent. To learn more visit http://www.werewolftx.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risk and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Werewolfs future operations, prospects, plans, the projection of the cash runway, the expected timeline for the clinical development of product candidates and availability of data from such clinical development, and the potential activity and efficacy of product candidates in preclinical studies and clinical trials constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words aim, anticipate, believe, contemplate, continue, could, design, designed to, estimate, expect, goal, intend, may, might, objective, ongoing, plan, potential, predict, project, promise, should, target, will, or would, or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the development of product candidates, including the conduct of research activities, the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and the Companys ability to submit and obtain regulatory approval for investigational new drug applications; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; the Companys ability to obtain sufficient cash resources to fund the Companys foreseeable and unforeseeable operating expenses and capital expenditure requirements; the impact of the COVID-19 pandemic on the Companys business and operations; as well as the risks and uncertainties identified in the Risk Factors section of the Companys most recent Annual Report on Form 10-K for the year ended December 31, 2021, filed with the Securities and Exchange Commission (SEC), and in subsequent filings the Company may make with the SEC. In addition, the forward-looking statements included in this press release represent the Companys views as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Companys views as of any date subsequent to the date of this press release.

Investor Contact:Josh RappaportStern IR212.362.1200Josh.rappaport@sternir.com

Media Contact:Peg RusconiVERGE Scientific Communicationsprusconi@vergescientific.com

Company Contact:Ellen LubmanChief Business OfficerWerewolf Therapeuticselubman@werewolftx.com

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Werewolf Therapeutics Reports First Quarter 2023 Financial Results ... - BioSpace

PeaceHealth cuts Bellingham jobs, announces clinic closure and reduces some services – Yahoo News

PeaceHealth, a Pacific Northwest not-for-profit health-care system, is closing a Bellingham clinic and ending certain services, resulting in the elimination of 32 local jobs.

Across PeaceHealths 10 communities it serves in Washington, Oregon and Alaska, and its headquarters in Vancouver, Washington, 251 positions have been eliminated, according to an email from Beverly Mayhew, senior director of marketing and communications for PeaceHealths northwest network.

In Bellingham, the 32 terminated positions come from changes in the Allergy & Immunology Clinic, the Sleep Lab and the Outpatient Palliative Care program.

The Allergy & Immunology Clinic will close permanently, although a date has not been chosen yet, according to Mayhew. The clinic at 4545 Cordata Parkway, Suite 1C, is not accepting new patients, and current patients can continue to receive care from the clinic until further notice.

We recognize that patients will require transition plans specific to their condition, physicians and clinic staff have prioritized patient needs and identified appropriate clinical options for each type of patient. The options for asthma and allergy care locally range from continuing with another allergist or with primary care providers.

Fortunately, there is an excellent community-based allergist at the Bellingham Asthma, Allergy & Immunology Clinic, and primary care providers at PeaceHealth Medical Group and other family medicine clinics are well versed in allergy care, Mayhews statement read.

Bellinghams Sleep Lab will also stop providing overnight sleep lab services on May 15, eliminating some jobs. The lab will still provide sleep consultations and home sleep studies, and will help patients find alternatives for overnight sleep lab services.

PeaceHealth is also eliminating some caregiver roles within the Outpatient Palliative Care program in Bellingham, but will continue to offer care for patients in various ways.

We will continue to support patients with complex care needs using a new model which includes care navigators, coupled with support from our home health team and, if appropriate, our hospice caregivers. Every effort will be made to minimize the impact to patients through this transition by identifying their specific needs and aligning appropriate services, Mayhew wrote.

PeaceHealth credits the job eliminations to the costs of health care rising slower than what it was earning for the care being provided, according to Mayhew.

To make sure that we can continue to sustain our mission into the future, we conducted a comprehensive review of all services and operations. The result is growth in some areas and reductions in others.

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PeaceHealth cuts Bellingham jobs, announces clinic closure and reduces some services - Yahoo News

Takeda reports 12.8% rise in FY2022 revenue – Pharmaceutical Technology

Takeda has reported a 12.8% increase in itsreportedrevenue to $29.96bn (Y4,027bn) during the fiscal year 2022 (FY2022) compared to that reported in FY2021.

At a constant exchange rate (CER), the companys core revenue grew by 3.5% compared to the previous year.

In the FY2022 ending 31 March 2023, the company also reported a 6.4% rise in its operating profit to $3.65bn (Y490.5bn) compared to 2021.

Reported earnings per share (EPS) grew by 38.8% to $1.5bn (Y204bn) and net profit for FY2021 increased by 37.8% to $2.36bn (Y317bn).

The same fiscal year recorded a 13% decline to $7.27bn (Y977.2bn) in operating cash flow.

The company has provided commercial updates across its five key business areas: gastroenterology (GI), rare diseases, plasma-derived therapy (PDT) immunology, oncology and neuroscience.

Its GI business reported an 8.7% increase in revenue to $8.145bn (Y1,094.5bn) on a CER basis.

Entyvio, for ulcerative colitis (UC) and Crohns disease (CD), steered the growth in the revenue of this business.

Rare diseases reported revenue growth of 4.8% to $5.38bn (Y723.4bn) and PDT immunology reported growth of 15.3% to $5.048bn (Y678.4bn), both on a CER basis.

Oncology reported a 14.4% decline in reported revenue on a CER basis to $3.26bn (Y438.7bn).

In neuroscience, reported revenue rose by 12.1% to $4.75bn (Y637.7bn) on a CER basis.

Takeda chief financial officer Costa Saroukos stated: Im pleased to report that Takeda delivered or exceeded management guidance in FY2022 and booked a record core operating profit of almost Y1.2tn.

Our topline and profit performance was driven by our growth and launch products, which grew 19% at a constant exchange rate.

Strong financial discipline and free cash flow have enabled us to deleverage rapidly while investing in growth.

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Takeda reports 12.8% rise in FY2022 revenue - Pharmaceutical Technology