Category Archives: Immunology

Immunology

Symposium explores health lessons learned from the pandemic – HSPH News

November 3, 2021 What lessons have scientific researchers learned from the COVID-19 pandemic? And how can they better apply them to the next major outbreak of disease? More than 200 participants gathered virtually to discuss those questions at Harvard T.H. Chan School of Public Healths 24th annual John B. Little Symposium, held on October 29, 2021.

The event honors the late John B. Little, who was the James Stevens Simmons Professor of Radiobiology Emeritus in Harvard Chan Schools Department of Molecular Metabolism. Little passed away in May 2020.

I vividly remember Jack always sat in the front row with undivided attention, said Zhi-Min Yuan, Morningside Professor of Radiobiology and director of the John B. Little Center for Radiation Sciences, who moderated the symposium. Jacks ongoing legacy stays with us, as we continue this highly received annual event.

In her opening remarks, Dean Michelle Williams introduced the theme of this years conference, COVID-19: Transformative Discoveries and Emerging Research Frontiers. Said Williams, Just as our personal lives have been upended for the past 20 months, so have been the professional lives of researchers. This disruption required really remarkable, profound adaptations that gave rise to new ideas. The diverse group of speakers for the symposium, she noted, shared a wide range of perspectives, including from molecular biology, epidemiological studies, and translational studies.

Among them was Eric Rubin, editor-in-chief of the New England Journal of Medicine and adjunct professor of immunology and infectious diseases at Harvard Chan School, who spoke on the difficulties of generating accurate data for treatment of COVID-19 in the early days of the pandemic. While as a clinician, Rubin said, he could understand the desire for clinicians to try some kind of therapy to address patients suffering, they often drew the wrong conclusions from incomplete early studies. He noted that hydroxychloroquine was widely used before it was shown to do nothing, remdesivir was widely used despite a very mild effect if any, and dexamethasone was virtually ignored. And that is one that worked! he said.

Very few of the millions of patients suffering from COVID-19 were involved in clinical studies, Rubin added, and many of the studies conducted during the pandemic were done on small groups of patients without coordination with one another. In the future, Rubin said, researchers must get better at leveraging existing infrastructure for clinical trials to coordinate studies much more rapidly. Its really important, even in the midst of an epidemic, to figure out whether or not what you are going to do is going to answer the question you care about, he said.

Other speakers at the symposium included the National Institutes of Healths Michele Evans, who spoke on health disparities during the pandemic; University of Iowa microbiology and immunology professor Stanley Perlman, who discussed breakthroughs on animal models for COVID-19; and University of Texas at Austin molecular biosciences professor Jason McLellan, who detailed techniques for identifying the SARS-CoV-2 spike protein that allowed for rapid development of vaccines.

Michael Blanding

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Symposium explores health lessons learned from the pandemic - HSPH News

Immunology

The tricks of lymphomas – EurekAlert

image:Immune cells can migrate into the lymph nodes via particularly large blood vessels (red and green in the picture) and destroy existing tumor cells (white). These vessels are gradually remodeled in aggressive non-Hodgkins lymphomas. This is probably why cell-based immunotherapies have so far not been effective against this type of tumor. view more

Credit: Rehm Lab, MDC

Cellular immunotherapies have so far not been very effective against non-Hodgkins lymphoma.A team led by Armin Rehm of the MDC has discovered a possible reason. As the they describe in Cell Reports, this cancer induces changes in the large blood vessels through which immune cells normally migrate to the lymph nodes.

Immunotherapies have become an indispensable part of modern cancer treatment. They are particularly effective against cancers like Hodgkins disease, a type of blood cancer that attacks the lymphatic system. When it comes to aggressive non-Hodgkins lymphomas, however, comparable approaches that employ various strategies to incite the immune system to attack the tumor cells typically end in failure.

Lymph node architecture is disrupted

The probable reason for this failure has now been uncovered by a team led by Dr.Armin Rehm, head of the Translational Tumor Immunology Lab at the Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC) in Berlin. In experiments with mice and human tumor tissue, we were able to show that the cancer cells disrupt the delicate architecture of the lymph nodes, explains Dr.Lutz Menzel, first author of the Cell Reportspaper and a researcher in Rehms lab.

This ultimately leads to a group of large blood vessels the high endothelial venules losing one of their most important functions. Without these intact vessels, immune cells cannot migrate into the lymph nodes on their patrols to track down tumor cells, explains Menzel. Several research groups at the MDC were involved in the German Cancer Aid-funded study, including the Microenvironmental Regulation in Autoimmunity and Cancer Lab led by Dr.Uta Hpken.

Identical findings in mice and humans

We knew from a previous study that aggressive lymphomas, such as diffuse large B-cell non-Hodgkins lymphoma, stimulate the growth of small capillary-like vessels in the lymph nodes, says Rehm. In this way the tumor cells ensure that they are optimally supplied with nutrients during their rapid growth. At the same time, microscopic examinations showed us that there were very few blood vessels with larger diameters in the affected lymph nodes, reports Rehm, adding that the findings in mice were identical to those in humans with aggressive lymphomas.

In the current study, the researchers first used mice to investigate how the loss ofhigh endothelial venulesoccurs, a situation that allows lymphomas to evade attack by the cellular immune system. We discovered a complex cascade of changes which include the scaffold structures in the lymph nodes being disrupted, says Menzel. Such disruption causes changes in the pressure and volume ratios, both of which influence gene expression.

This, he says, eventually leads to high endothelial venules being transformed into completely normal blood vessels, thus cutting off the immune cells access to the cancer cells. The team was then able to confirm these observations in human cancer tissue. They examined nearly 80tissue samples from patients with aggressive non-Hodgkins lymphoma to validate the results.

Cancer cells create protective niches for themselves

Many types of tumors employ strategies to evade an attack by the immune system, says Rehm. For example, cancer cells develop special surface molecules or produce signaling molecules that shut down immune cells. Little research had been done previously on how lymphomas protect themselves from the bodys defenses as they grow. Our study now provides deeper insights into the methods tumor cells use to create protective niches in lymph nodes, notes Rehm.

It is crucial to know what is happening in the tumor microenvironment, especially when it comes to cancer immunotherapy, adds Menzel. Only in this way can we devise strategies that enable therapeutic Tcells to reach the tumor site, where they can fight the tumor directly.

Easing immune cell immigration

The team plans to use the new findings to develop targeted strategies to halt or even reverse the process responsible for the disappearance of high endothelial venules. One thing we are trying to do is specifically alter the vessels in the lymph nodes with the help of various drugs, says Rehm. The goal here, he says, is to ease immune cell immigration and prevent tumor cells from shielding themselves against attack in their niches. In this way the researchers hope that immunotherapeutic approaches like CAR T-cell therapy may also become more effective against aggressive non-Hodgkins lymphomas.

Further information

Translational Tumor Immunology Lab

A potent weapon against lymphomas

Lymphomas different route revealed

Max Delbrck Center for Molecular Medicine (MDC)

The Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC) is one of the worlds leading biomedical research institutions. Max Delbrck, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the MDCs locations in Berlin-Buch and Mitte, researchers from some 60 countries analyze the human system investigating the biological foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium in a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should benefit as soon as possible from basic research discoveries. The MDC therefore supports spin-off creation and participates in collaborative networks. It works in close partnership with Charit Universittsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charit, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the MDC today employs 1,600 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.www.mdc-berlin.de

Experimental study

Lymphocyte access to lymphoma is impaired by high endothelial venule regression

26-Oct-2021

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The tricks of lymphomas - EurekAlert

Immunology

Prokarium Promotes Livija Deban to Chief Scientific Officer to Drive Pipeline Expansion in Cancer Immunotherapy – Business Wire

LONDON--(BUSINESS WIRE)--Prokarium, a biopharmaceutical company pioneering the oncology field of microbial immunotherapy, today announced the appointment of Livija Deban, PhD, as Chief Scientific Officer.

Since joining Prokarium, Livija has been central to the strategic and operational development of the companys immuno-oncology portfolio, including our next-generation Salmonella platform, said Kristen Albright, PharmD, Chief Executive Officer of Prokarium. I look forward to closely working with her and the team to establish Prokarium as a recognized leader in microbial immunotherapy.

At Prokarium, we are leveraging cutting edge science at the intersection of immunology and synthetic biology to develop innovative therapies for the treatment of solid tumors, said Dr. Deban. Our approach builds on the long history of microbial immunotherapy and holds the promise of providing solutions to many clinical needs that cannot be addressed by current cancer therapeutics. I am honored to be appointed as CSO and am excited to work with the leadership team and the board to accelerate our pipeline.

Dr. Deban previously served as Prokariums Vice President of Research. Prior to joining Prokarium, she led the immuno-oncology R&D at Oxford BioTherapeutics, where she focused on the target discovery and the development of antibodies for cancer treatment. Previously, Dr. Deban conducted her postdoctoral academic research at Cancer Research UK and Kings College London. She received her masters degree in Medical Biotechnology from the University of Bologna and holds a PhD in Basic and Applied Immunology from University Vita-Salute San Raffaele, Italy.

About Prokarium

Prokarium is a biopharmaceutical company pioneering the field of microbial immunotherapy. Our pipeline is designed to unlock the next level of immuno-oncology by building on the most recent advances in cancer immunology. Prokariums lead program is focused on transforming the treatment paradigm in bladder cancer by orchestrating immune-driven, long-lasting antitumor effects. Prokarium is based London, UK. For further information, visit https://www.prokarium.com.

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Prokarium Promotes Livija Deban to Chief Scientific Officer to Drive Pipeline Expansion in Cancer Immunotherapy - Business Wire

Immunology

Inflammatory Mediator Could Be Targeted To Treat Pneumonia – Technology Networks

Researchers at Karolinska Institutet in Sweden report that a recently discovered inflammatory mediator, interleukin-26, appears to have an important role in pneumonia and contribute to the killing of bacteria. The study is published in the scientific journalFrontiers in Immunology - Microbial Immunology.Bacterial lung infection affects both children and adults worldwide and pneumonia remains a common cause of premature death in many parts of the world, with millions of people dying from it every year. To facilitate the development of more effective therapies, researchers at Karolinska Institutet are trying to characterise the immunological mechanisms involved in pneumonia.

The new study demonstrates that an inflammatory mediator called interleukin-26 (IL-26) is critically involved in bacterial pneumonia in humans. During the last decade, IL-26 has emerged as an important player in the so-called innate immune response, our first line of defence against pathogens. It is abundant in the airways of healthy humans, and bacterial exposure stimulates an increased release of IL-26 by lung cells and white blood cells.

Studying human lung tissue and airway samples from patients with bacterial pneumonia, the researchers were able to show that IL-26 exerts complex modulatory effects on the immune system and that the protein directly kills bacteria known to cause pneumonia.

Antibiotics are not sufficient to treat pneumonia and antibiotic resistance is an increasing problem, highlighting the need for biological treatments of this global killer disease. Our findings position IL-26 as a new potential target for biological treatment and emphasise that its role in pneumonia deserves to be further evaluated, says lead author Karlhans Che, a researcher at the Institute of Environmental Medicine, Karolinska Institutet.

The research was financed by the Swedish Heart-Lung Foundation, The Swedish Research Council, Region Stockholm (ALF funding), and The Swedish Society for Medical Research. The authors declare that there is no conflict of interest.

Reference:Che KF, Paulsson M, Piersiala K, et al. Complex involvement of interleukin-26 in bacterial lung Infection. Front. Immunol. 2021;12:4531. doi: 10.3389/fimmu.2021.761317

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Inflammatory Mediator Could Be Targeted To Treat Pneumonia - Technology Networks

Immunology

Merck and Synthekine Strike $525 Million Cytokine Therapy Deal – BioSpace

Merckis widening its reach into the treatment of autoimmune diseases by investing inSynthekine, a bioresearch company that develops engineered cytokine therapeutics.

Under a worldwidecollaboration and research agreement, Merck can exclusively take advantage of Synthekine's surrogate cytokine agonist platform to discover, develop, and sell new cytokine-based treatments for up to two cytokine targets. The companies will first look into potential therapies for autoimmune illnesses but can later go into immunology, oncology, and other indications.

Cytokines are small proteins that are essential to immune homeostasis, but developing them to create therapies can be tricky due to their pleiotropic nature. Trying to harness them for treatment often leads to "wild-type" products that have either dose limiting toxicities or low efficacy. However, using Synthekine's technology, cytokine agonists can dimerize or multimerize cytokine receptors properly, resulting in a wide range of biased and selective signaling potential.

"At Synthekine, we are focused on advancing cytokine science through three protein engineering platforms to create optimized therapeutics in this important space. Our surrogate cytokine agonist platform produces a new class of cytokine therapeutics that are designed to deliver selective immunotherapies for the treatment of autoimmune diseases and cancer," said Debanjan Ray, chief executive officer of Synthekine, in a statement.

Merck will pay Synthekine upfront, plus another one-time payment if a second target is identified. Synthekine stands to receive as much as $525 million in milestones and royalties from net sales for every target achieved. Funding for research will also come from Merck.

"Emerging insights from immunology and oncology are providing new and different ways to think about treating diseases. We look forward to collaborating with Synthekine to evaluate new approaches to harness the therapeutic potential of cytokines," added Dr. Dean Y. Li, the president of Merck Research Laboratories.

Just a few days ago, Synthekine announced that the U.S. Food and Drug Administrationapproved its investigational new drug (IND) application forSTK-012, an IL2 partial agonist that has the potential for use as monotherapy or in combination with immune checkpoint inhibitors to treat advanced solid tumors. STK-012 has the ability to stimulate antigen-activated T cells, which are linked with anti-tumor activity while avoiding the stimulation of toxicity-causing killer cells.

IL-2 is a cytokine with proven benefit as an anti-cancer therapy. However, the indiscriminate activity of IL-2 can cause severe toxicities, limiting its clinical application. We have designed STK-012 to uncouple the efficacy and toxicity of IL-2, and we look forward to now investigating its potential in our first clinical development program," noted Naiyer Rizvi, M.D., the chief medical officer of Synthekine, in a separate press release.

Synthekine is expected to begin its clinical investigation for SK-012 soon.

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Merck and Synthekine Strike $525 Million Cytokine Therapy Deal - BioSpace

Immunology

Pfizer bows out of the Tyk2 race – Vantage

2021 had once looked like the year of the Tyk2 inhibitors, but some shine is coming off this member of the Jak family. Pfizer today disclosed plans to offload two projects with activity against Tyk2, not long after the lead proponent of this approach, Bristol Myers Squibb, reported disappointing data with deucravacitinib in ulcerative colitis. Pfizer did not give a reason for its Tyk2 exit, which will see brepocitinib and PF-06826647 licensed to a new company that Pfizer is forming in partnership with an unnamed autoimmune player; the pharma giant will have a 25% stake in this venture and retain certain ex-US rights. Perhaps the decision was spurred by toxicity concerns with the Jak inhibitors, which solidified in September into a class warning; however, Pfizer is keeping hold of its Jak1 abrocitinib which is still awaiting an FDA decision in atopic dermatitis and the Jak3/Tec inhibitor ritlecitinib. Still, other mechanisms now look like a priority: Pfizer highlighted several immunology projects in its third-quarter presentation, including a high potency topical PDE4 inhibitor, PF-07038124, for atopic dermatitis and psoriasis; PF-06480605, a TL1A inhibitor for ulcerative colitis; and the interferon-beta Inhibitor PF-06823859 in dermatomyositis.

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Pfizer bows out of the Tyk2 race - Vantage

Immunology

Gossamer Bio to Announce Third Quarter 2021 Financial Results and Host Conference Call and Webcast on November 8, 2021 – marketscreener.com

Gossamer Bio, Inc. (Nasdaq: GOSS), a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, today announced that it will report its third quarter 2021 financial results on Monday, November 8, 2021.

In connection with the earnings release, Gossamers management team will host a live conference call and webcast at 4:15 p.m. ET on Monday, November 8, 2021, to discuss the Companys financial results and provide a corporate update.

Conference ID: 9749597Domestic Dial-in Number: (833) 646-0603International Dial-in Number: (929) 517-9782Live Webcast: https://edge.media-server.com/mmc/p/sezfo9jk

A replay of the audio webcast will be available for 30 days on the Investors section of the Company's website, http://www.gossamerbio.com.

About Gossamer Bio

Gossamer Bio is a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology. Its goal is to be an industry leader in each of these therapeutic areas and to enhance and extend the lives of patients suffering from such diseases.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211102006184/en/

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Gossamer Bio to Announce Third Quarter 2021 Financial Results and Host Conference Call and Webcast on November 8, 2021 - marketscreener.com

Immunology

Rising to the COVID-19 Challenge: Using Preclinical Models to Assess Vaccines and Antivirals, Upcoming Webinar Hosted by Xtalks – PR Web

SRI International has utilized their biosafety level 3 (BSL3) facilities and mobilized its virology and immunology groups to develop preclinical and in vitro COVID-19 models.

TORONTO (PRWEB) November 02, 2021

Given the enormity of the COVID-19 pandemic, researchers are pursuing multiple drug, immune therapy and vaccine development strategies. SRI, as one of NIHs leading preclinical partners, has a long history of rapid response to critical issues like COVID-19. To help address this new viral challenge, SRI International has utilized their biosafety level 3 (BSL3) facilities and mobilized its virology and immunology groups to develop preclinical and in vitro COVID-19 models.

Using these novel models, they have the ability to test novel antiviral approaches against multiple SARS-CoV-2 strains, including the Delta strain. For example, they can partner with a wide variety of companies to screen their novel biologics for activity against SARS-CoV-2 variants in their own in vitro assays. Within months of the pandemic, SRI scientists determined in vivo LD50 infection curves and used these parameters to best assess anti-viral compounds.

These assays can generate realistic data to guide the development of robust antiviral approaches to eliminate the pandemic threat. SRI is working with scientists from around the world to create practical antiviral treatments that will be used for years. Additionally, they are working to develop and validate rapid in vitro testing platforms to screen for SARS-CoV-2 exposure and infection.

Join Mary Lanier, PhD, Director of Immunology and Virology, SRI Biosciences, A Division of SRI International, in a live webinar on Thursday, November 18, 2021 at 1pm EST (10am PST) to hear more about these preclinical models including the data they have generated and how they are working with partners to improve preclinical modeling for COVID-19 therapeutics and vaccines.

For more information, or to register for this event, visit Rising to the COVID-19 Challenge: Using Preclinical Models to Assess Vaccines and Antivirals.

ABOUT XTALKS

Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global life science, food and medical device community. Every year, thousands of industry practitioners (from life science, food and medical device companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers.

To learn more about Xtalks visit http://xtalks.comFor information about hosting a webinar visit http://xtalks.com/why-host-a-webinar/

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Rising to the COVID-19 Challenge: Using Preclinical Models to Assess Vaccines and Antivirals, Upcoming Webinar Hosted by Xtalks - PR Web

Immunology

UConn Immunology Researcher Unraveling Relationship Between Cytokines and Colorectal Cancer – UConn Today – UConn Today

Kepeng Wang, assistant professor of immunology at UConn Health, is investigating the complex relationship between cytokines and colorectal cancer.

Wangs work is supported by a $1.8 million grant from the National Cancer Institute.

Cytokines are a category of proteins secreted by cells. They have an important role in cell signaling. IL-17 cytokines, one family of cytokines, promote inflammation which drives the growth of tumors on the colon. This often leads to colorectal cancer.

To date, the underlying mechanism explaining IL-17s connection with colorectal cancer relies on its role in helping the tumor recruit myeloid cells, which come from bone marrow. This provides the tumor with a powerful ally to help it grow and spread throughout the body.

What scientists do not yet fully understand is if IL-17 also signals regulatory T cells (Tregs). Tregs are often recruited to tumors and hinder the bodys natural ability to impede tumor growth.

Wangs preliminary studies show that removing IL-17 signaling on Treg cells increased colonic tumor development in mice. This demonstrated a previously unknown protective role of IL-17 in colorectal cancer, indicating its relationship with tumorigenesis and growth is more complicated than previously thought.

Wangs team found that IL-17 inhibits Treg accumulation in tumors, a measure that typically indicates a grim prognosis. IL-17 also inhibits the expression of genes that facilitate Treg migration, proliferation, and their ability to suppress the immune system.

Interestingly, Wangs team only observed these inhibitory effects in tumor-infiltrating Tregs and not in healthy Tregs. This suggests IL-17 engages in site-specific inhibition. Accordingly, only Tregs that infiltrate tumors express the receptors IL-17 cytokines attach to in order to initiate this cascade.

When Wang stimulated Tregs with two cytokines that are abundant in the tumor environment, it led to increased production of the IL-17 receptor. This suggests when Tregs are recruited to tumors, the tumors environment makes it more susceptible to being inhibited by IL-17.

Conversely, Wang and his team found that IL-17 signals to tumor cells to reduce the expression of cytokines that signal CD8+ CTL T cells to the tumor. These T cells play an important role in immunity and tumor surveillance. These cytokines are known as CXCL9 and CXCL10.

This means IL-17 inhibits Tregs that would otherwise suppress cancer immunosurveillance while also inhibiting the attraction of T cells that would perform this function. These findings illuminate the complicated role of IL-17 in colorectal cancer and showcase the need for further investigation.

Now, Wang is looking to further his previous work and clarify IL-17s role in colorectal cancer.

Wang will describe how, exactly, IL-17 mediates the direct inhibition of Tregs in colorectal tumors as well as identify the underlying molecular mechanisms of this process. Wang will then interrogate how IL-17 inhibits T cell attraction through the regulation of CXCL9 and CXCL10.

Ultimately, Wang will test the importance of these interactions and effects in colorectal tumor development and therapies.

These investigations will provide new insights into the mechanisms by which IL-17 impacts colorectal tumorigenesis, as well as guide the invention and use of novel therapies for the treatment of colorectal, Wang says.

For example, understanding how IL-17 inhibits CD8+ CTL T cell attraction to tumors could mean adding already available IL-17 antibodies to cancer immunotherapy regimes would improve patient outcomes. While, if a tumor has abundant IL-17 and Tregs, researchers and clinicians could know that using IL-17 antibodies may have an adverse effect for the patient since IL-17 is performing a protective role in this case.

This work can help provide a pathway toward more precise treatments for colorectal cancer patients.

Wang holds a Ph.D. in biochemistry from Hong Kong University of Science and Technology. Wangs lab focuses on studying the role of inflammation in colorectal cancer development and therapeutic intervention.

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