Category Archives: Immunology

Eli Lilly Signs Development Deal for Novel Immunology Drug – Drug Discovery & Development

Eli Lilly is bolstering its autoimmune offerings with a new co-development and commercialization agreement.

The deal will focus on a promising drug called NKTR-358, developed by Nektar Therapeutics. Its being designed to target the interleukin (IL-2) receptor complex in the body in an effort to stimulate the proliferation of regulatory T-cells. Activating these cells could bring the immune system back into balance.

As part of this agreement, Nektar will receive an initial payment of $150 million from Eli Lilly with the potential to receive an estimated $250 million if the drug achieves certain development and regulatory milestones, according to the announcement.

Investigators achieved the first human dose of NKTR-358 as part of a Phase I clinical trial in March 2017 with the goal of measuring observed changes and functional activity of regulatory T cells in approximately 50 healthy patients.

Both companies will co-develop NKTR-358 with Nektar being responsible for completing Phase 1 clinical development, but then the costs will shift for Phase 2 in which Lilly will handle 75 percent and Nektar the remaining 25 percent.

Furthermore, Nektar will be able to receive double-digit royalties that increase based on its Phase III investment and product sales with Lilly handling all costs of global commercialization.

"We are very pleased to enter into this collaboration with Lilly as they have strong expertise in immunology and a successful track record in bringing novel therapies to market," said Nektars President and CEO Howard W. Robin, in a statement. Importantly, this agreement enables the broad development of NKTR-358 in multiple autoimmune conditions in order to achieve its full potential as a first-in-class resolution therapeutic."

Proving this drugs mechanism of action is viable could ultimately yield a multi-purpose therapy that could work for autoimmune conditions like lupus and psoriasis.

Excerpt from:
Eli Lilly Signs Development Deal for Novel Immunology Drug - Drug Discovery & Development

Dak Prescott: Great Guy Who Gets Pumped to Bad Music – D Magazine

It pains me to write this post, because Dak Prescott seems fairly unimpeachable character-wise. Especially after reading this Sports Illustrated interview, in which last years Rookie of the Year talks about his effort to raise $150,000 to bolster awareness to immunology research in the wake of his mothers death from cancer in 2013. He also dings Zeke for his ESPN the Magazine Body Issue cover, saying he should use his platform to do things like Im doing such asthis cancer campaign instead of doing his thing for the body issue and doing photo shoots.

Side-eye notwithstanding, look at that character!

I wish Id stopped reading there.SI just had to include this tidbit:

SI:Favorite song right now?

Prescott:My favorite song ever isDrops of Jupiterby Train. Its one of the songs I listen to before games. Its chill, but its also upbeat at the same time.

But, you know what, if that gets him going, Cowboys fans cant really complain too much. Maybe thats why he seems so calm in the pocket.Anyway, head here to learn more about the Ready. Raise. Rise. campaign that Prescotts aligning withtoraise money for immunology research; its a dual effort with Bristol-Myers Squibb.

Here is the original post:
Dak Prescott: Great Guy Who Gets Pumped to Bad Music - D Magazine

A few drops of blood lead to a breakthrough in immunology – Radio Canada International

Not the sun, but a microscopic look at a specific gene in a specific cell that has led to a major advance in our understanding and treatment of auto-immune diseases. Photo Credit: Ciriaco Piccirillo, Research Institute of the McGill University Health Centre

It was one of those tragic cases in medicine.

A newly born child, just weeks old, had a severe auto-immune condition that could not be treated and which led irrevocably to his death.

With just a few drops of the childs blood, researchers led by a team in McGill University and the Research Institute-McGill University Health Centre (RI-MUHC) in Montreal, have painstakingly discovered the cause in a subset of so-called T-cells, and have created a solution that has major disease treatment implications.

Dr. Ciriaco Piccirillo led an international research team with input from the USA and Japan. He is an immunologist and senior scientist with the Infectious Diseases and Immunity in Global Health Programat the Research Institute-McGill University Health Centre (RI-MUHC), and a Professor of Immunology and Medicine at McGill University. He is also the Director of the newly created Centre of Excellence in Translational Immunology (CETI) at the RI-MUHC.

The baby boy died in 2009 of a rare and often fatal inherited genetic immune disorder called IPEX. The case involved the childs T-cells, and specifically the Treg cell, the immunosuppressive cells of the immune system.

These latter are a special kind of white blood cells or lymphocytes that regulate the bodies auto-immune response. They prevent other immune cells from attacking the bodys own tissues, as well as controlling immune responses against microbes and other non-pathogenic agents, such as pollen, dust or benign food groups. This is an important self-check built into the immune system to prevent excessive reaction.

When the immune response is not controlled it can cause damage to the body in diseases such as rheumatoid arthritis, Lupus, and Crohns disease as well as broader conditions such as asthma, allergies and cancer.

Through meticulous molecular research and availability of new highly sophisticated technology at the RI-MUHC, the team was able to determine a defect in a particular gene in the Treg cell which prevented it from properly acting in its regulatory role in dampening the immune system response.

Certain genes, but especially the FOXP3 gene are responsible for programming so-to-speak a T-cell to become a Treg cell.

What the team found from the babys blood was a rare mutation of the FOXP3 gene which negatively impacted its capacity to promote Treg cell development and function in humans.

After the intense research to detect the genetic defect in the specific FOXP3 gene, they developed a drug which appears able to correct the genetic defect resulting in an almost completely normally functioning Treg cell.

The teams research was published in the online journal Science-Immunology under the title Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions (abstract HERE)

Further, while this should work in those rare patients with IPEX, professor Piccirillo says the team in now working on improving the drug to bolster its effects on the FOXP3 gene and developing Treg cells in other inflammatory and autoimmune diseases.

He says this likely will have far greater treatment possibilities in relation to a number of auto-immune diseases which are typically very difficult to treat.

The study was funded by the Canadian Institutes of Health Research, Canada Research Chair Program, National Institutes of Health and the Abramson Family Cancer Research Institute.

Go here to see the original:
A few drops of blood lead to a breakthrough in immunology - Radio Canada International

Constitutive resistance to viral infection in human CD141 – Science (subscription)

Research ArticleDENDRITIC CELLS

* These authors contributed equally to this work.

Present address: INSERM U955, IMRB Equipe-16, VRI, F-94010, Creteil, France.

Present address: Drukier Institute for Childrens Health, Weill Cornell Medical College, New York, NY 10021, USA.

+ See all authors and affiliations

Science Immunology 07 Jul 2017: Vol. 2, Issue 13, eaai8071 DOI: 10.1126/sciimmunol.aai8071

Aymeric Silvin

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Chun I Yu

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.The Jackson Laboratory, Bar Harbor, ME 04609, USA.

Xavier Lahaye

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Francesco Imperatore

Centre dImmunologie de Marseille-Luminy, Aix Marseille University, UM2, INSERM U1104, CNRS UMR7280, France.

Jean-Baptiste Brault

Institut Curie, PSL Research University, CNRS, UMR144, Molecular Mechanisms of Intracellular Transport, 75005 Paris, France.

Sylvain Cardinaud

Centre dImmunologie et des Maladies Infectieuses-Paris, Pierre and Marie Curie University UMRS C7, INSERM U1135, CNRS ERL 8255, Paris, France.INSERM U955, IMRB Equipe-16, Vaccine Research Institute (VRI), F-94010, Creteil, France.

Christian Becker

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine; and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.

Wing-Hong Kwan

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Ccile Conrad

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Mathieu Maurin

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Christel Goudot

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Santy Marques-Ladeira

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Yuanyuan Wang

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

Virginia Pascual

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

Esperanza Anguiano

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

Randy A. Albrecht

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Matteo Iannacone

Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Adolfo Garca-Sastre

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Bruno Goud

Institut Curie, PSL Research University, CNRS, UMR144, Molecular Mechanisms of Intracellular Transport, 75005 Paris, France.

Marc Dalod

Centre dImmunologie de Marseille-Luminy, Aix Marseille University, UM2, INSERM U1104, CNRS UMR7280, France.

Arnaud Moris

Centre dImmunologie et des Maladies Infectieuses-Paris, Pierre and Marie Curie University UMRS C7, INSERM U1135, CNRS ERL 8255, Paris, France.

Miriam Merad

Precision Immunology Institute, Human Immune Monitoring Center, Tisch Cancer institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

A. Karolina Palucka

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.The Jackson Laboratory, Bar Harbor, ME 04609, USA.

Nicolas Manel

Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.

Read more from the original source:
Constitutive resistance to viral infection in human CD141 - Science (subscription)

How a Few Drops of Blood Led to An Immunology Breakthrough – Drug Discovery & Development

Scientists from the Research Institute of the McGill University Health Centre (RI-MUHC) may have cracked the code to understanding the function of special cells called regulatory T Cells. Treg cells, as they are often known, control and regulate our immune system to prevent excessive reactions. The findings, published in Science Immunology, could have a major impact in our understanding and treatment of all autoimmune diseases and most chronic inflammatory diseases such as arthritis, Crohns disease as well as broader conditions such as asthma, allergies and cancer.

Researchers made this discovery by investigating a rare human mutation in a gene called FOXP3. Although the importance of the FOXP3 gene in the proper function of Treg cells has been well documented, its mechanisms were still not fully understood by scientists.

We discovered that this mutation in the FOXP3 gene affects the Treg cells ability to dampen the immune response, which results in the immune system overreacting and causing inflammation, explains the studys lead author, Dr. Ciriaco Piccirillo, immunologist and senior scientist in the Infectious Diseases and Immunity in the Global Health Program at the RI-MUHC, and a professor of Immunology at McGill University. This discovery gives us key insights on how Treg cells are born and how they can be regulated.

Thanks to an international collaboration and cutting-edge technology from the Immunophenotyping Platform at the RI-MUHC, the team was able to make their discovery using only a few drops of blood from a five-week-old newborn boy who died in 2009 from a rare and often fatal inherited genetic immune disorder called IPEX. In the past 40 years, fewer than 200 cases of IPEX have been identified worldwide. Over 60 different mutations of the FOXP3 gene are known to cause IPEX and believed to result in non-functional Treg Cells.

What was unique about this case of IPEX was that the patients Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response, says Dr. Piccirillo.

Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions, adds the studys first author, Khalid Bin Dhuban, a postdoctoral fellow in Dr. Piccirillos laboratory.

From fundamental biology to clinical treatment

Dr. Piccirillo and his colleagues have already developed a molecule that could restore the Treg cells' ability to control the immune system for patients with the same rare mutation. The drug has been tested in animal models and the researchers are hopeful they can also develop similar drugs that will apply for other conditions where Treg cells are known to be slightly defective such as arthritis, type I diabetes, multiple sclerosis and lupus.

"Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," explains Dr. Piccirillo. Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer. With this discovery, we are taking a big step in the right direction.

Dr. CiriacoPiccirillo is also the director of theCentre of Excellence in Translational Immunology (CETI), a newly established research coalition based at the Research Institute of the MUHC that fosters linkages among biomedical investigators and clinicians for interdisciplinary immunology research focused on the understanding and treatment of immune-based diseases.

View post:
How a Few Drops of Blood Led to An Immunology Breakthrough - Drug Discovery & Development

How a few drops of blood led to a breakthrough in immunology – Medical Xpress

July 5, 2017 The image shows a lymph node in which we see normal T cells (in red) and Treg cells regulated by the FOXP3 gene (in green). Lymph nodes are small glands that are part of the lymph system which is important for body's defense system against diseases. Technique used: Confocal microscopy Credit: Ciriaco Piccirillo, Research Institute of the McGill University Health Centre

Scientists from the Research Institute of the McGill University Health Centre (RI-MUHC) may have cracked the code to understanding the function of special cells called regulatory T Cells. Treg cells, as they are often known, control and regulate our immune system to prevent excessive reactions. The findings, published in Science Immunology, could have a major impact in our understanding and treatment of all autoimmune diseases and most chronic inflammatory diseases such as arthritis, Crohn's disease as well as broader conditions such as asthma, allergies and cancer.

Researchers made this discovery by investigating a rare human mutation in a gene called FOXP3. Although the importance of the FOXP3 gene in the proper function of Treg cells has been well documented, its mechanisms were still not fully understood by scientists.

"We discovered that this mutation in the FOXP3 gene affects the Treg cell's ability to dampen the immune response, which results in the immune system overreacting and causing inflammation," explains the study's lead author, Dr. Ciriaco Piccirillo, immunologist and senior scientist in the Infectious Diseases and Immunity in the Global Health Program at the RI-MUHC, and a professor of Immunology at McGill University. "This discovery gives us key insights on how Treg cells are born and how they can be regulated."

Thanks to an international collaboration and cutting-edge technology from the Immunophenotyping Platform at the RI-MUHC, the team was able to make their discovery using only a few drops of blood from a five-week-old newborn boy who died in 2009 from a rare and often fatal inherited genetic immune disorder called IPEX. In the past 40 years, fewer than 200 cases of IPEX have been identified worldwide. Over 60 different mutations of the FOXP3 gene are known to cause IPEX and believed to result in non-functional Treg Cells.

"What was unique about this case of IPEX was that the patient's Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response," says Dr. Piccirillo.

"Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions," adds the study's first author, Khalid Bin Dhuban, a postdoctoral fellow in Dr. Piccirillo's laboratory.

From fundamental biology to clinical treatment

Dr. Piccirillo and his colleagues have already developed a molecule that could restore the Treg cells' ability to control the immune system for patients with the same rare mutation. The drug has been tested in animal models and the researchers are hopeful they can also develop similar drugs that will apply for other conditions where Treg cells are known to be slightly defective such as arthritis, type I diabetes, multiple sclerosis and lupus.

"Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," explains Dr. Piccirillo. Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer. With this discovery, we are taking a big step in the right direction."

Dr. Ciriaco Piccirillo is also the director of the Centre of Excellence in Translational Immunology (CETI), a newly established research coalition based at the Research Institute of the MUHC that fosters linkages among biomedical investigators and clinicians for interdisciplinary immunology research focused on the understanding and treatment of immune-based diseases.

Explore further: Preventing too much immunity

More information: Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions, Science Immunology 16 Jun 2017: Vol. 2, Issue 12, eaai9297 , DOI: 10.1126/sciimmunol.aai9297 , http://immunology.sciencemag.org/content/2/12/eaai9297

An immune-related protein deployed between neighboring cells in Drosophila plays an essential role in the cell degradation process known as autophagy, according to new research by Eric H. Baehrecke, PhD, at UMass Medical ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Continued here:
How a few drops of blood led to a breakthrough in immunology - Medical Xpress

Sun Pharma agrees manufacturing deal for immunology candidate – The Pharma Letter (registration)

India's largest drugmaker Sun Pharmaceutical has entered into a manufacturing agreement with South Koreas

To continue reading this article and to access exclusive features, interviews, round-ups and commentary from the sharpest minds in the pharmaceutical and biotechnology space you need to be logged into the site and have an active subscription or trial subscription. Please loginorsubscribe in order to continue reading. Claim a week's trial subscriptionby signing up for free today and receive our daily pharma and biotech news bulletin free of charge, forever.

BiotechnologyDealsImmunologicalsIndiaProductionSamsung BioLogicsSouth KoreaSun Pharmaceutical Industriestildrakizumab

Access The Pharma Letter's latest news free for 7 days

PLUS... you can receive the Pharma Letter headlines and news roundup email free forever

Click here to take a free trial

Unlimited access to The Pharma Letter site for a whole year Only 77 per month or 820 per year

Click here to subscribe

Read more:
Sun Pharma agrees manufacturing deal for immunology candidate - The Pharma Letter (registration)

Immunology, one cell at a time : Nature News & Comment – Nature.com

Amir Giladi & Ido Amit

Single-cell genomics can identify unique immune cells (red) involved in Alzheimer's disease.

For more than a century, scientists have tried to characterize the different functions of the 10 trillion to 50 trillion cells of the human body from neurons, which can reach 1 metre in length, to red blood cells, which are around 8 micrometres wide. Such efforts have helped to identify important cell types and pathways that are involved in human physiology and pathology.

But it has become apparent that the research tools of the past few decades fail to capture the full complexity of cell diversity and function. (These tools include fluorescent tags fused to antibodies that bind to specific proteins on the surfaces of cells, known as cell-surface markers, and sequencing in bulk of the RNA or DNA of thousands of seemingly identical cells.) This failure is partly because many cells with completely different functions have similar shapes or produce the same markers.

Single-cell genomics is transforming the ability of biologists to characterize cells. The new techniques that have emerged aim to capture individual cells and determine the sequences of the molecules of RNA and DNA that they contain. The shift in approach is akin to the change in how cells and molecules could be viewed during the 1980s, following advances in microscopy and the tagging and sorting of cells.

In the past five years, several groups of biologists, including our own laboratory, have gone from measuring the expression of a few genes in a handful of cells to surveying thousands of genes in hundreds of thousands of cells from intact tissues. New cell types1, 2, cellular states and pathways are being uncovered regularly as a result.

Our lab was one of the first to study the immune system using single-cell genomics. The tools are particularly suited to this task because the heterogeneity and plasticity of cells are integral to how the immune system works the nature of each agent that could attack the body being impossible to know ahead of time.

Exploiting single-cell genomics fully will require scientists and clinicians to make experimental and analytical adjustments. In particular, we must be ready to jettison assumptions about cell types and cellular states, and to rebuild representations of cellular networks.

The cells of the immune system, which patrol the blood and dwell in tissues, have many functions. They protect the body from pathogens and cancer, and orchestrate metabolism and the formation of organs. They are involved in almost every activity that regulates the bodys internal environment, from the development and remodelling of tissues to the clearance of dying cells and debris. So their dysfunction can cause many problems. For instance, deregulated immune cells can attack healthy cells and cause autoimmune conditions such as lupus, type 1 diabetes or multiple sclerosis.

A first step towards harnessing the immune system for therapeutic use is to characterize the types of cell that occupy a specific area (such as the surroundings of a tumour). Another is to map the unique processes and pathways that the cells are involved in, the genes they express and the cells interactions and responses to environmental cues. Over the past 40 years, meticulous approaches based on genetic labelling have enabled researchers to identify dozens of types and functions of immune cells. For example, the use of antibodies fused to fluorescent tags that bind to and flag specific cell-surface markers established the basic taxonomy of immune cells including several types of T cells, B cells, monocytes and granulocytes. Such studies also kick-started the search for treatments known as immunotherapies, which harness the body's natural defences to fight disease.

Increasingly, however, these techniques hint that the world of immune cells is more complex than current categories allow. Immune cells seem to change their functions depending on their surroundings. For instance, macrophages (as identified by their cell-surface markers) might have one function in the gut yet a completely different one in the brain3. Also, molecular markers cannot fully describe the functional diversity of cells in different immune contexts. For example, a group of immune cells that suppresses the immune response around tumours (myeloid-derived suppressor cells) has been shown to express markers from both monocytes and granulocytes4.

In short, conventional methods based on populations of cells are proving too blunt a tool with which to tease apart complex immune assemblies5.

In the past five years, technologies for capturing single cells have improved dramatically. Some approaches rely on placing cells inside miniature vessels, one at a time; others capture individual cells inside droplets of oil. Meanwhile, bioinformaticians have built algorithms for representing multidimensional data, identifying distinct cellular states and modelling the transitions between such states6.

Thanks to these developments, researchers can now capture hundreds of thousands (or even millions) of cells and accurately measure the DNA, RNA or protein content of each (see Scale up). Gene-editing tools such as the CRISPRCas9 system can be used to introduce a specific mutation into the genome of one cell, and then a different alteration into the next7. Thus, the function of dozens of genes can be inferred from just one experiment by reading the resulting RNA barcode in parallel with the single-cell genetic information.

With such measurements, researchers can potentially record the functional states of many cells at once8. They can also probe the ancestry of individual cells9 or identify mutations in a particular cells DNA, as well as track communication between cells. In other words, single-cell genomics allows researchers to build an accurate representation of the entire make-up of a tissue10, such as a specific organ or a tumour, or of a multicellular process such as the immune systems response to an infection. Importantly, it enables them to do this without making prior assumptions based on, for instance, the participating cell types and their characteristics.

About 20 labs worldwide have fully embraced single-cell genomics, and even more are trying out the approach. In the past few years, numerous papers have been published that describe new types of immune cell and previously unknown pathways involved in various conditions.

For instance, 15 subtypes of innate lymphoid cell, which are similar to T cells but do not express the T-cell receptor, have been identified in the gut11. Different progenitors of immune-cell lineages have been uncovered in the bone marrow12. Specific types of immune cell have been associated with particular stages of tumour growth13, 14. And various types of microglial cell have been identified in the brain during development.

Last month, our lab reported the discovery of a new type of immune cell in the brain, disease-associated microglia (DAM)15. Our experiments indicate that DAM break down dead cells and protein aggregates called plaques in the brains of mice engineered to express mutated proteins associated with Alzheimers disease.

More than a decade of population-based assays, including cell sorting using specific cell-surface markers and bulk RNA sequencing, had failed to flag these cells. Only by individually sequencing the RNA of each of the immune cells in a sample of brain were we able to find a rare subpopulation of microglia that may open up fresh approaches to treating Alzheimers disease.

It is early days for single-cell genomics. But already, a number of important lessons can be learnt from the experiences of our lab and those of others.

First, it is clear that many of the current categories of immune cells, such as T cells or monocytes, encompass heterogeneous populations. To probe cellular complexity, researchers must therefore cast their nets wide, and try to collect all immune cells within a tissue or region of interest. This is a very different approach from that used with methods based on cell-surface markers, which aim to obtain as pure a sample as possible.

Second, success will depend, in part, on the extent to which researchers preserve the states of cells and the original composition of a tissue. Cell stress or death should be minimized to ensure that tissue preparation does not favour specific cell types. (Some are more sensitive to heat stress, for example, than others.)

Single-cell genomics will soon be commonplace in basic and applied immunology research.

Third, bioinformaticians will need to develop scalable and robust algorithms to cope with greater numbers of cells, conflicting or overlapping programs of gene expression and fleeting developmental stages.

Fourth, after researchers have characterized all of the immune cells in a sample, they will need to find molecular markers that can be used to either enrich or deplete certain cell types in further samples. Tissues comprise trillions of cells with myriad molecular characteristics and functions, and the types or states of these cells may vary in abundance by many orders of magnitude. For instance, in the brains of healthy mice, our newly identified population of DAM makes up less than 0.01% of cells15. Thus, repeated unbiased sampling to characterize rare populations will keep on accumulating cells that are not those of interest.

Other experimental, computational and statistical approaches can help to overcome this problem. Importantly, once a rare population of cells is identified using single-cell genomics, they can be purified and experiments conducted only on them. In our recent study, for instance, we used cell-surface markers to isolate DAM and then assessed their role in Alzheimers disease using various techniques, including fluorescent labelling.

A fifth lesson regards a considerable drawback of current single-cell technologies. They capture snapshots of dynamic systems, in which cells are devoid of important context spatial, temporal, clonal and epigenetic. Without knowing where a profiled cell came from, who its neighbours were or what it developed from, it is hard to model complex processes such as tissue formation or a tumours interaction with nearby immune cells.

One way around this problem might be to combine several layers of information from the same cell. Genetic fluorescent labelling, for instance, can be used to track changes in the state of a cell over time or to find exactly where it is in a tissue.

Ultimately, textbook definitions and long-held beliefs about cellular identities, such as the distinction between cell type and cell state, will almost certainly need to be rethought. Some classifications of subgroups based on extra markers may prove helpful in the short term, but can quickly become unwieldy. For example, instead of being able to refer to T-helper (TH) cells, researchers must now refer to one of about a dozen subcategories, including TH1 cells and TH2 cells16. And such an approach may continue to overlook the true functional complexity of the immune ecosystem.

A more workable solution may be for researchers to replace rigid classifications with assemblies of gene-expression programs (see Genetic microscope). These elaborate gene maps could represent all cell types and states, including those from different physiological and pathological contexts. Such maps would allow biologists to define cells not just by one fate, lineage or function, but by the combination of all of these. It would also allow these functional entities to be compared across organisms.

Claire Welsh/Nature

Single-cell genomics will soon be commonplace in basic and applied immunology research. This is thanks to efforts to make the tools affordable, standardized and accessible to academia, the biotech industry and the clinic. We predict that, within a decade, blood samples or biopsies will be routinely sent for single-cell genomic analysis, and the entire immune composition of patients analysed and compared with all known healthy and diseased states.

Also likely to undergo rapid transformation is our understanding of tumours and tumour stem cells, processes such as neuronal development, metabolic disorders and neural function.

Almost every scientific breakthrough has originated from a new measurement or observation that enabled scientists to come up with new hypotheses and merge them into unifying theories. Robert Hookes observation of cells as units of multicellular organisms, James Watson and Francis Cricks discovery of the 3D structure of DNA and Edwin Hubbles detection of galaxies beyond the Milky Way could not have been achieved without new ways of seeing.

The molecular microscope of single-cell genomics is already adding to our knowledge of cell types and gene pathways. But for single-cell genomics to tell us something truly new about the blueprint of humans, we will have to address how individual cells communicate to achieve shared goals.

Here is the original post:
Immunology, one cell at a time : Nature News & Comment - Nature.com

Sansum Allergy/Immunology Department Moving – Noozhawk

Posted on June 30, 2017 | 9:00 a.m.

On Monday, July 17, the Sansum Clinic Allergy & Immunology Department will move to 51 Hitchcock Way in Santa Barbara. The new location is adjacent to Sansum's Pediatrics and Adolescent Medicine Department.

The Allergy & Immunology Department offers comprehensive care for children and adults with allergic and immunologic disorders, including the following:

Immunotherapy (allergy shots); pediatric and adult pulmonary testing; allergy blood and skin testing; patch skin testing; oral challenge testing; drug testing; lab and x-ray services.

The entrance to the new department is on Hitchcock Way, across the street from the YMCA and accessible from Highway 101 or State Street. The practice will be on the first floor.

To learn more about Sansum Clinic, visit http://www.sansumclinic.org.

Elizabeth Baker for Sansum Clinic.

Visit link:
Sansum Allergy/Immunology Department Moving - Noozhawk

Merck’s Immunology and Cardiovascular Franchise in 1Q17 – Market … – Market Realist

Merck & Co.s Recent Developments and Valuations PART 10 OF 11

Merck & Co.s (MRK) Immunology franchise includes Remicade and Simponi. Remicade is one of the top-selling drugs for the treatment of inflammatory disorders, while Simponi is a once-monthly subcutaneous treatment. Both drugs reported a decline in revenues during 1Q17.

Remicades revenues fell ~34% to $229 million in 1Q17, compared to $349 million for 1Q16. This decline was due to the entry of generic competition and biosimilars following the loss of exclusivity of Remicade in the European markets in February 2015. Merck expects Remicades revenues to continue their declines, as new patients prefer biosimilars over Remicade.

While Merck has the marketing rights for Remicade in the European markets, Johnson & Johnson (JNJ) holds marketing rights of Remicade in several countries outside Europe.

Simponis revenues fell to $184 million in 1Q17, compared to $188 million in 1Q16.

Mercks Cardiovascular franchise includes the blockbuster drugs Zetia and Vytorin. These drugs are used for lowering the LDL cholesterol levels in the blood of patients with a high risk of cardiovascular disease.

The combined revenues for Zetia and Vytorin fell 35% to $575 million in 1Q17, compared to $889 million in 1Q16. Zetia competes with AbbVies (ABBV) Niaspan and Pfizers (PFE) Lipitor.

To divest company-specific risks, investors can consider the iShares Core High Dividend ETF (HDV), which holds ~3.5% of its total assets in Merck. HDV also holds 4.9% in Pfizer (PFE) and 1.5% in Eli Lilly & Co. (LLY).

Read the original:
Merck's Immunology and Cardiovascular Franchise in 1Q17 - Market ... - Market Realist