Category Archives: Immunology

Immunology

HI-Bio Announces $95 Million Series B Financing to Advance Targeted Therapies for Immune-Mediated Diseases – PR Newswire

Funding allows advancement of diverse programs through multiple clinical data readouts, including multiple indications for lead candidatefelzartamab

SOUTH SAN FRANCISCO, Calif., Jan. 4, 2024 /PRNewswire/ --Human Immunology Biosciences (HI-Bio), a clinical-stage biotechnology company developing targeted therapies for patients withsevere immune-mediated diseases (IMDs), today announced the closing of a $95 million Series B financing led by new investor Alpha Wave Global. Viking Global Investors and Arkin Bio Capital participated in the financing, as well as existing investors Jeito Capital and ARCH Venture Partners.

"These funds allow us to advancefelzartamab, our clinically differentiated lead therapeutic candidate, through clinical readouts in multiple indications and preparation for registrational studies," said Travis Murdoch, M.D., CEO of HI-Bio. "We are encouraged by promising clinical data to date for felzartamab and its anti-CD38 cell depletion approach, and we look forward to new data, including Phase 2 results from an investigator-initiated trial for antibody-mediated rejection in kidney transplant patients."

Since the company's launch, HI-Bio has advancedfelzartamab, a monoclonal antibody targeting CD38 and in-licensed from MorphoSys, across indications including antibody-mediated rejection (AMR), IgA nephropathy (IgAN), lupus nephritis (LN) and primary membranous nephropathy (PMN). Felzartamab has received Breakthrough Therapy Designation and Orphan Drug Designation from the U.S. Food and Drug Administration in PMN. HI-Bio has also initiated a clinical study of HIB210, an anti-C5aR1 candidate targeting neutrophil activation and chemotaxis.

"Immune-mediated diseases contribute to an immense disease burden which drives the need for novel targeted treatments to improve on existing therapies," said Chris Dimitropoulos, Managing Director of Healthcare Investments at Alpha Wave Global. "HI-Bio is generating compelling clinical data demonstrating the differentiated potential of felzartamab; we look forward to continued progress for felzartamab across multiple indications with high unmet need."

Funding from the Series B will be used to advance clinical development offelzartamab, to evaluate the clinical properties of HIB210 in healthy volunteers and to advance a discovery-stage program targeting mast cell dysfunction toward IND-enabling studies. In conjunction with the financing, the company announced that Chris Dimitropoulos, Managing Director of Healthcare Investments at Alpha Wave Global, has been appointed to the HI-Bio Board of Directors.

About HI-Bio Human Immunology Biosciences, Inc. (HI-Bio) is a clinical-stage biotechnology companyfocused on discovering and developing precision medicines for people suffering from immune-mediated diseases (IMDs). HI-Bio is leading clinical immunology into its next chapter by targeting cellular drivers of disease. To learn more about HI-Bio, visit us at http://www.hibio.com or follow us on LinkedIn and Twitter.

SOURCE HI-Bio

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HI-Bio Announces $95 Million Series B Financing to Advance Targeted Therapies for Immune-Mediated Diseases - PR Newswire

Immunology

Beyond Cytotoxicity: The Importance of T Cell Memory – The Scientist

This webinar will be hosted live and available on-demand

Thursday, January 25, 2024 2:30-4:00 PM Eastern Time

B cells are the classical shield bearers of immune system memory, but memory T cell phenotypes also exist, playing crucial roles in controlling viral infections and modulating immune responses.

In this webinar brought to you by The Scientists Creative Services Team, Grgoire Lauvau and Marcus Buggert will explain what memory T cells are, how they differ from cytotoxic T cells, and their function in human tissues during physiological and pathological situations.

Topics to be covered

Grgoire Lauvau, PhD Professor The Sylvia and Robest Olnick Faculty Scholar in Cancer Research Albert Einstein College of Medicine Department of Microbiology and Immunology

Marcus Buggert, PhD Assistant Professor Karolinska Institutet Department of Medicine Huddinge Center for Infectious Medicine (CIM)

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Beyond Cytotoxicity: The Importance of T Cell Memory - The Scientist

Immunology

IKAROS: Unlocking the secrets of the immune system’s key player – News-Medical.Net

In a scientific breakthrough that aids our understanding of the internal wiring of immune cells, researchers at Monash University in Australia have cracked the code behind IKAROS, an essential protein for immune cell development and protection against pathogens and cancer.

This disruptive research, led by the eminent Professor Nicholas Huntington of Monash University's Biomedicine Discovery Institute, is poised to reshape our comprehension of gene control networks and its impact on everything from eye colour to cancer susceptibility and design of novel therapies.

The study, published in Nature Immunology, promises pivotal insights into the mechanisms safeguarding us against infections and cancers. When the transcription factor Ikaros/Ikzf1 was deliberately obstructed, be it in preclinical models or humans, the once-mighty activity of Natural Killer (NK) cells, our immune system's frontline warriors, plummeted. Loss of this transcription factor in NK cells resulted in wide-spread dysregulation of NK cell development and function, preventing their ability to recognize and kill virus-infected cells and clear metastatic tumour cells from circulation. Aiolos/Ikzf3 and Helios/Ikzf2, related family member were found to partial compensate for the loss of Ikaros, as such when multiple IKZF-family members were inhibited, NK cells underwent rapidly death. Mechanistically, Aiolos and Ikaros were found to directly bind and activate most members of the JUN/FOS family, transcription factors known for their essential roles in human embryo development and tissue function.

This discovery opens the door to the prospect of potential novel cancer therapeutics. NK cells, our first line of defence against pathogens and internal threats like cancers, could be fortified by therapies enhancing their killing prowess by targeting IKAROS and JUN/FOS biology.

Professor Huntington notes that drugs targeting IKAROS/AIOLOS have already received approval from the US Food and Drug Administration (FDA) and local Therapeutic Goods Administration (TGA) for the treatment of B cell malignancy "but until now we haven't understood how these drugs work, armed with this new information it could be possible to develop novel drugs targeting these complexes which may offer differentiated pharmacology and therapeutic index for treating disease," he said.

Importantly on this front, Professor Huntington's team were able to show that IKAROS had a conserved role in healthy B cells and thus potentially B cell cancers.

Source:

Journal reference:

Goh, W., et al. (2024). IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development. Nature Immunology. doi.org/10.1038/s41590-023-01718-4.

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IKAROS: Unlocking the secrets of the immune system's key player - News-Medical.Net

Immunology

UCLA to turn former shopping mall into centers for research on immunology and quantum science – The Caledonian-Record

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UCLA to turn former shopping mall into centers for research on immunology and quantum science - The Caledonian-Record

Immunology

Revolutionizing Vaccine Research: The Power of a New Algorithm – SciTechDaily

Immunology researchers have introduced a computational tool to improve pandemic preparedness by enabling the comparison of diverse experimental data. This algorithm uses machine learning to find patterns in datasets, enhancing the understanding of immune responses. It promises significant advances in vaccine design and immunology research, with broad potential in various biological contexts.

Computational biologists harness machine learning to make sense of immune system data.

Immune system researchers have designed a computational tool to boost pandemic preparedness. Scientists can use this new algorithm to compare data from vastly different experiments and better predict how individuals may respond to disease.

Were trying to understand how individuals fight off different viruses, but the beauty of our method is you can apply it generally in other biological settings, such as comparisons of different drugs or different cancer cell lines, says Tal Einav, Ph.D., Assistant Professor at La Jolla Institute for Immunology (LJI) and co-leader of the new study in Cell Reports Methods.

This work addresses a major challenge in medical research. Laboratories that study infectious diseaseeven laboratories focused on the same virusescollect wildly different kinds of data. Each dataset becomes its own independent island, says Einav.

Some researchers might study animal models, others might study human patients. Some labs focus on children, others collect samples from immunocompromised senior citizens. Location matters too. Cells collected from patients in Australia might react differently to a virus compared with cells collected from a patient group in Germany, just based on past viral exposures in those regions.

Theres an added level of complexity in biology. Viruses are always evolving, and that changes the data too, says Einav. And even if two labs looked at the same patients in the same year, they might have run slightly different tests.

La Jolla Institute for Immunology (LJI) Assistant Professor Tal Einav, Ph.D. Credit: Matthew Ellenbogen, La Jolla Institute for Immunology

Working closely with Rong Ma, Ph.D., a postdoctoral scholar at Stanford University, Einav set out to develop an algorithm to help compare large datasets. His inspiration came from his background in physics, a discipline whereno matter how innovative an experiment isscientists can be confident that the data will fit within the known laws of physics. E will always equal mc2.

What I like to do as a physicist is collect everything together and figure out the unifying principles, says Einav.

The new computational method doesnt need to know precisely where or how each dataset was acquired. Instead, Einav and Ma harnessed machine learning to determine which datasets follow the same underlying patterns.

You dont have to tell me that some data came from children or adults or teenagers. We just ask the machine how similar are the data to each other, and then we combine the similar datasets into a superset that trains even better algorithms, says Einav. Over time, these comparisons could reveal consistent principles in immune responsespatterns that are hard to detect across the many scattered datasets that abound in immunology.

For example, researchers could design better vaccines by figuring out exactly how human antibodies target viral proteins. This is where biology gets really complicated again. The problem is that humans can make around one quintillion unique antibodies. Meanwhile, a single viral protein can have more variations than there are atoms in the universe.

Thats why people are collecting bigger and bigger data sets to try and explore biologys nearly infinite playground, says Einav.

But scientists dont have infinite time, so they need ways to predict the vast reaches of data they cant realistically collect. Already, Einav and Ma have shown that their new computational method can help scientists fill in these gaps. They demonstrate that their method to compare large datasets can reveal myriad new rules of immunology, and these rules can then be applied to other datasets to predict what missing data should look like.

The new method is also thorough enough to provide scientists with confidence behind their predictions. In statistics, a confidence interval is a way to quantify how certain a scientist is of a prediction.

These predictions work a bit like the Netflix algorithm that predicts which movies you might like to watch, says Einav. The Netflix algorithm looks for patterns in movies youve selected in the past. The more movies (or data) you add to these prediction tools, the more accurate those predictions will get.

We can never gather all the data, but we can do a lot with just a few measurements, says Einav. And not only do we estimate the confidence in predictions, but we can also tell you what further experiments would maximally increase this confidence. For me, true victory has always been to gain a deep understanding of a biological system, and this framework aims to do precisely that.

Einav recently joined the LJI faculty after completing his postdoctoral training in the laboratory of Jesse Bloom, Ph.D., at the Fred Hutch Cancer Center. As he continues his work at LJI, he plans to focus on the use of computational tools to learn more about human immune responses to many viruses, beginning with influenza. Hes looking forward to collaborating with leading immunologists and data scientists at LJI, including Professor Bjoern Peters, Ph.D., also a trained physicist.

You get beautiful synergy when you have people coming from these different backgrounds, says Einav. With the right team, solving these big, open problems finally becomes possible.

Reference: Using interpretable machine learning to extend heterogeneous antibody-virus datasets by Tal Einav and Rong Ma, 25 July 2023, Cell Reports Methods. DOI: 10.1016/j.crmeth.2023.100540

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Revolutionizing Vaccine Research: The Power of a New Algorithm - SciTechDaily

Immunology

Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people … – Nature.com

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Immunology

Two new practice parameters offer recommendations for treating anaphylaxis and atopic dermatitis – News-Medical.Net

Two new practice parameters from the Joint Task Force for Practice Parameters (JTFPP) offer evidence-based recommendations for the diagnosis and management of anaphylaxis and atopic dermatitis (AD) in pediatric and adult patients. The Joint Task Force is a partnership between the American College of Allergy, Asthma and Immunology (ACAAI) and the American Academy of Allergy, Asthma and Immunology.

Both anaphylaxis and atopic dermatitis are allergic conditions that affect millions of people in the United States and around the world. We regularly update our practice parameters to make sure allergists and other healthcare practitioners are aware of best practices when diagnosing and managing these disorders. When physicians and their staffs are aware of updated guidance, it means patients are getting the best, most appropriate care."

Jay Lieberman, MD, allergist, co-chair of the JTFPP Task Force

"The 2023 JTFPP anaphylaxis practice parameter provides evidence-based recommendations to support optimal contextual care across contemporary practice settings," says allergist David B.K. Golden, MDCM, lead author of the practice parameter. "With important new guidance related to diagnostic evaluation, anaphylaxis in infants and in community settings, epinephrine treatment, mast cell conditions, beta-blockers and ACE inhibitors, and peri-operative anaphylaxis, these guidelines translate recent advances in the understanding of severe allergic reactions to help all healthcare professionals provide individualized care to each patient at the right time, in the right place, every time."

The practice parameter on anaphylaxis focuses on areas where new evidence has emerged, and recommendations have evolved.

Key anaphylaxis guideline highlights include:

"The 2023 JTFPP atopic dermatitis guideline represents an advancement in trustworthy allergy guidelines," says allergist Derek Chu, M.D., Ph.D. "It is distinguished from other guidelines through systematic reviews of the evidence with multidisciplinary panelist engagement, adherence to GRADE a rigorous guideline development process, as well as the involvement of the patient and caregiver voice from start to finish. Clear translation of evidence to clinically actionable and contextual recommendations, and novel approaches to facilitate knowledge translation were paramount. The guidelines emphasize, in addition to standards of trustworthiness, the third principle of evidence-based medicine: that evidence alone is never enough; that patient values and preferences are crucial to arriving at optimal recommendations. The new recommendations also reflect the evolution of diversity, equity and inclusion in approaching diagnosis and management of this condition."

Key atopic dermatitis guideline highlights include:

The practice parameters are published in Annals of Allergy, Asthma & Immunology, the scientific journal of the American College of Allergy, Asthma & Immunology.

Source:

Journal reference:

Sacta, M. A., et al. (2023). Anaphylaxis: A 2023 practice parameter update. Annals of Allergy Asthma & Immunology. doi.org/10.1016/j.anai.2023.10.027.

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Two new practice parameters offer recommendations for treating anaphylaxis and atopic dermatitis - News-Medical.Net

Immunology

Physician and Patient (Un)Wellness in Allergy and Immunology During COVID-19 and Beyond: Lessons for the Future – Physician’s Weekly

The following is a summary of Allergy and Immunology Physician and Patient (Un)Wellness During COVID-19 and Beyond: Lessons for the Future, published in the November 2023 issue of Allergy and Clinical Immunology by Bingemann, et al.

The COVID-19 outbreak made both patients and doctors more stressed and less healthy. Uncertainty, regular changes, fear of getting sick or dying, and problems with the supply chain put extra stress on a healthcare system that was already broken. Control, regularity, and confidence make for a good workplace. The outbreak took away these things. During this time, the number of depressed, suicidal, and anxious doctors and people in the general population went up. These problems got worse because people had different ideas about masks and vaccines.

These things, along with how much people felt appreciated or not, also made stress worse. Some changes, like switching to video, were stressful initially, but they made patients happy and kept clinical care going. Some changes could have been better, like teaching or watching young children while working. Both patients and doctors did their best to deal with loneliness, fear, worry, and the many changes in society. During the pandemic, burnout changed depending on the number of infections, the number of vaccinations, problems with the supply chain, and the amount of support given to each person.

The pandemic brought to light problems in their healthcare system, such as structural racism, differences in healthcare, and how quickly the system can become overloaded. Doctors may have been put in positions they didnt want to be in or may need more staff to practice how they wanted. Patients and doctors both got angry because of these things. In its National Plan for Health Workforce Well-Being, the government says that health care needs to be reformed so that patients can get good, safe care and doctors dont get burned out.

Source: sciencedirect.com/science/article/abs/pii/S2213219823009273

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Physician and Patient (Un)Wellness in Allergy and Immunology During COVID-19 and Beyond: Lessons for the Future - Physician's Weekly

Immunology

Researchers Identify Why Some Cancers Do Not Respond to Immunotherapy – NYU Langone Health

Over the last decade, immune checkpoint blockade has transformed cancer care by offering new hope and improved outcomes for people with certain types of cancer. However, immune checkpoint blockade, a type of cancer immunotherapy that enhances the bodys natural immune response against tumor cells, is only effective in 20 to 30 percent of patients with cancer. And people with some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance to the immunotherapy.

A recent study by researchers at NYU Langone Healths Perlmutter Cancer Center could lead to new strategies for improving the effectiveness of immune checkpoint inhibitors. The researchers identified an axis or pathway that tumor cells use to shut down the function of a key molecule called major histocompatibility complex (MHC) class I. Under normal conditions, MHC class I enables the immune system to detect and eliminate cells that have been transformed or infected.

Study senior co-author Jun Wang, PhD, a cancer immunologist, has a background in viral immunology. Through his earlier studies of viruses and the immune system, he knew that viruses are able to shut down MHC class I to evade T cell response. What if, he asked, cancer cells can do the same?

We know that viruses can very efficiently shut down MHC class I and evade the immune system, said Dr. Wang, who is an assistant professor in the Department of Pathology at NYU Grossman School of Medicine. How tumors can shut down MHC class I has not been clear at all.

The immune system recognizes and eliminates infected or mutated cells through a process called antigen presentation. During antigen presentation, intracellular pathogens, such as viruses and certain bacteria, or abnormal cellular proteins, such as those from cancer cells, are transported by MHC class I molecules and presented to killer T cells, which are activated and mount an immune response.

With study senior co-author Iannis Aifantis, PhD, and co-first authors Xufeng Chen, PhD (Aifantis Lab), and Qiao Lu, PhD (Wang Lab), Dr. Wang used a gene editing technology called CRISPR to screen for new cellular activators and inhibitors of antigen presentation in AML. Among the top hits in the CRISPR screen were three proteins: sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and an E3 ubiquitin ligase WWP2. The researchers found that SUSD6 forms a trimolecular complex with TMEM127 and MHC class I, which recruits WWP2 to initiate the degradation of MHC class I and ultimately leads to suppression of MHC class I expression.

When the researchers deactivated SUSD6, which is abundantly expressed in AML and several other solid cancers, antigen presentation by MHC class I was improved and tumor growth was reduced in cell cultures.

We were able to show that if we genetically target this particular complex, we boost the expression of MHC class I with more antigen on the surface and have better recognition by T cells, said Dr. Aifantis, who is the Hermann M. Biggs Professor of Pathology in and chair of the Department of Pathology at NYU Grossman School of Medicine.

Immune checkpoint inhibitors have been particularly ineffective against cold tumors, which do not attract large numbers of immune cells. The trimolecular complex Dr. Wang and his colleagues identified is highly expressed on cold tumors, which suggests that the complex, in addition to being a new target for developing antibodies or small molecules that block its function, could act as a biomarker to help predict which patients will benefit from immunotherapy.

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Researchers Identify Why Some Cancers Do Not Respond to Immunotherapy - NYU Langone Health

Immunology

MU’s Haval Shirwan recognized for achievements in immunology – Columbia Daily Tribune

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MU's Haval Shirwan recognized for achievements in immunology - Columbia Daily Tribune