Category Archives: Immunology

Immunology

New success in treating allergies to peanuts and other foods – Science News for Students

Ten years ago at a kindergarten party, Isaac Judy took abite of a peanut-butter cookie. It tasted weird to him, so he spit it out. Hivessoon appeared on his face. His lips also began to swell. When his dad came topick him up, Isaac was coughing and wheezing. Riding in the car to the otherside of St. Louis, Mo., where they lived, Isaac fell asleep or so it seemed.

When Isaacs mother saw what was happening, she suspectedsomething more serious. He hadnt fallen asleep. He lost consciousness, JaelitheJudy explains. After a trip to the emergency room, her five-year-old recovered.But doctors confirmed her hunch: Isaac has a peanut allergy.

Just a few generations ago, hardly anyone talked about foodallergies. But over the past two decades, childhood food allergies in the UnitedStates have more than doubled. A little more than a year ago, a studyin Pediatrics reported that 7.6 percent of U.S. kids under age 18 havefood allergies. Thats almost 8 million youth about two students per classroom.And its much more than a childhood issue. Surprisingly, a studylast year in JAMA Network Open found that nearly 11 percent ofadults have food allergies, too. More than one in every four of them said they hadnot been allergic to foods as children.

These days nearly everyone has come across a family member orperson who has been touched by food allergies, or has one themselves,says Tamara Hubbard. She works in the suburbs of Chicago, Ill., as a licensedcounselor. Hubbard and a growing number of counselorsare helping families through the stress of managing food allergies.

For years, doctors have told families theres nothing they can do but avoid the trigger food or inject a fast-acting medication called epinephrine (Ep-ih-NEF-rinn) to stop a severe reaction. But researchers are learning more about why some people overreact to certain foods. And new treatments are emerging. Late last month, the first treatment for peanut allergy earned approval from the U.S. Food and Drug Administration. Another could do so within a year or so. Scientists also are continuing to develop and test other ways to treat food allergies.

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Allergic reactions occur when the immune system overreacts.Normally immune cells help fight bacteria, viruses and other pathogens. Yetsome peoples immune systems also react to harmless stuff like pollen or mold or peanuts, milk or other foods.

Such run-ins trigger a release of histamine (HIS-tuh-meen) and other chemicals. These molecules get the ball rolling for an allergic reaction, explains Tina Sindher. She works as an allergist at Stanford University School of Medicine in Palo Alto, Calif.

During an allergic reaction, someone may get itchy anddevelop hives. If the reaction worsens, the person might cough, wheeze andsuffer a whole-body reaction known as anaphylaxis(An-uh-fuh-LAX-iss). Thats what happened to Isaac and to Shea Tritts son,Gaines, in Abingdon, Va.

Gaines peanut allergy surfaced in the fall of 2012. At thetime, he was a baby and his diagnosis put the whole family on edge. For thenext few years he never trick-or-treated. He never went to a birthday party. Iwas scared to put him in preschool, says Tritt. My husband and I had a lot ofstress because he could tell I wasnt letting Gaines do normal things. So wewould argue.

Even Gaines older sister got nervous. If she went to aparty, she worried about bringing back traces of peanut-containing treats that mightsicken her brother, Tritt recalls. Living in such constant vigilance can be emotionallydraining for families with food allergies.

Anxious and desperate, Tritt wondered if her son would outgrow his allergies, and how she could ever find out. I became obsessed with information anything I could do to get us out of this situation, she says.

One day, Tritt saw a TV interview with David Stukus. Hes an allergist at Nationwide Childrens Hospital in Columbus, Ohio. Stukus saw that many patients with food allergy are fearful. They often are confused because theyre not getting the facts they need. So Stukus opened a Twitter account to spread evidence-based information. Tritt took note.

Looking at her sons blood-test results, year after year, Trittsuspected his immune response to peanuts was lessening. However, blood testscannot give a clear yes or no. These tests detect specialized immuneproteins. They are called IgE antibodies. These molecules trigger allergicreactions. But IgE levels only indicate that someone is sensitive to a certainfood. They cannot predict whether that person will react if they eat it. ProvingGaines had outgrown his peanut allergy would require an oral food challenge. And that would require that the patient eatincreasing amounts of the food while a doctor watches for allergicreactions.

Trouble is, Tritt could not find a local allergist toperform the food challenge. This procedure needs extra time and staff. It also runsa risk of triggering anaphylaxis. So, many clinics wont offer it unless apatients blood results are low low enough to suggest they would tolerate thefood. Gaines numbers had steadily dropped over the years but were still a tadtoo high.

For about half of people with peanut allergies, a bite or two of the wrong food typically contains enough peanut protein to trigger a reaction, notes Brian Vickery. He is a pediatric allergist at Emory University in Atlanta, Ga. For these people, he says, 100 milligrams (0.004 ounce) of peanut protein, or about one-third of a peanut kernel, can set off such a reaction.

Vickery used to work at Aimmune Therapeutics. ThisCalifornia company is developing a treatment for peanut allergy. It is calledoral immunotherapy, or OIT for short. The procedure involves each day eating awee bit of peanut protein pre-measured into capsules. The capsule dose goesup every few weeks over a period of months. If the treatment works, it canraise the immune systems threshold for the food. That means it would take moreof the food to trigger an allergic reaction. In other words, its possible for theperson to become bite-proof.

Aimmune tested its capsules or a dummy version called a placebo in 551 children and teens with peanut allergies. The starting dose was half a milligram (0.00002 ounce) of peanut protein. (One peanut contains 600 times that much.) Over a six-month period, the daily dose went up to 300 milligrams (0.01 ounce), or about one peanuts worth. And each day for six more months, participants had to continue eating that much.

During the study, many participants experienced allergicreactions to the peanut pills. Forty-five quit because of these unpleasantsymptoms. But among those who finished the study, two-thirds of the treatedgroup became bite-proof. After about a year, they could safely eat roughlytwo peanuts. Theyre still careful about avoiding peanuts, saysVickery. But it provides that additional margin of safety.

Those results appearedin the November 2018 New England Journal of Medicine.

Based on these and other findings, the FDA approved thosepeanut capsules on January 31.

Over the past decade and prior to the FDA approval, a small number of allergists had already started offering OIT using store-bought foods. Tritt found one such clinic several hours away. However, that clinic was not willing to give her son a peanut challenge to confirm whether he still was allergic.

Tritt didnt want to sign her son up for a long, costlytreatment if he might in fact be outgrowing his allergy.But they couldntknow for sure without the gold-standard test, that oral food challenge.

She discussed her dilemma with Stukus on Twitter. ReviewingGaines blood-test results, Stukus agreed to conduct the food challenge. Justbefore Gaines started kindergarten, his family travelled from Virginia to thedoctors clinic in Ohio. It was a nine-hour drive.

Gaines started the challenge with a small, laughableamount of peanut butter, Tritt recalls. Fifteen minutes later, he ate a bitmore. Then some more. Over several hours he chomped a dozen Reeses peanutbutter cups. And he never reacted.

The test proved Gaines had outgrown his allergy. That makeshim one of the lucky few. Many children outgrow some food allergies by the timethey enter school. But eight out of every 10 kids with allergies to peanuts or treenuts will remain allergic.

Gian Lagemann, a high school senior in Saratoga, Calif., isallergic to 11 kinds of nuts, including peanuts (which actually is not a nut; its a legume). When hestarted kindergarten, his mother brought no nuts allowed signs to theclassroom. She asked other parents to tell her whenever they brought in food so she could make sure it was safe for Gian. Every day Gian ate his lunch at adesignated peanut-free table.

Several years ago, Gians mom told her son about a peanutOIT trial. The study was starting nearby at Stanford University. For most ofmy life, I havent been able to eat things where the ingredient labels say maycontain peanuts or processed in a facility with peanuts, Gian says. Onceshe explained that [after the trial] Id be able to eat those foods, I waspretty happy. I was sold.

At the start of the trial, his family bought a bag of peanut flour. For about six months, Gian took his dose each day after dinner. He doesnt like the taste of peanuts. So he often mixed his dose into a spoonful of chocolate ice cream. The dose started at 1.3 milligrams of peanut protein (about 1/200th the amount in a peanut). Over the six-month trial it went up to 240 milligrams (0.008 ounce, or a little less than one peanuts worth).

More broadly, some 8,000 U.S. patients havetried such an oral therapy. Typically, about one in five will withdraw becauseof side effects or anxiety. Completing such a trial takes focusand discipline like playing sports. But, Gian recalls, They told us withevery dose we took, our body was just going to get stronger.

Participants also learned to expect some allergic reactions.If youre going to build your immune muscle against a food allergy, you knowyoure going to have a little ache during the process, says Kari Nadeau. ThisStanford allergist was a leader of the trial.

Gian felt a few such responses during the study. My throat would feel a little tight for 15 minutes, he says. But after that, it was fine. So he persevered. And it paid off. When the trial ended, he could eat a full peanut without having an allergic reaction. That means Gian now can safely eat candy with labels warning theyre made in facilities that process nuts. I was able to try Kit Kats for the first time, and Milky Ways, Gian says.

Two years ago, Isaac also tried this oral peanuttherapy. At the time, he was 13. But his experiences were quite different.During the treatment he suffered sinus and gastrointestinal troubles. He alsohad an anaphylactic reaction. Six months in, Isaac dropped out. He quit becausehe had developed an immune condition called eosinophilicesophagitis (Ee-oh-sin-oh-FILL-ick Ee-SOF-uh-JY-tis). The oral therapy triggersit in a small share of people.

And theres something else to keep in mind:People could lose their desensitization to peanut once they end the oraltherapy. That finding was confirmed in a 2019 study by Nadeaus team. Formany people, effective treatment might have to continue long-term.

Some people have taken part in research trialstesting a different treatment for peanut allergy a skin patch. Instead ofeating bits of peanut by mouth, patients every day stick a coin-sized disc ontotheir back or upper arm. Each disc contains a quarter-milligram of peanutprotein. Thats about a thousandth as much as whats in a peanut. (Bycomparison, Aimmunes capsules start with twice that much. Over months,patients then take doses that increase to 1, 10, 20, 100 and 300 milligrams.)From the patch, peanut proteins seep through the skin but do not enter theblood. Peanut patches are therefore less likely to cause anaphylaxis than is theoral therapy.

DBV Technologies in France makes the patch. This company conducted a year-long trial of its product in 356 children with peanut allergies. Nine in every 10 participants finished the trial. The most common side effect was a skin rash at the patch site. However, this trial didnt work as well as the company had hoped. By the end of the study, only a little more than one in every three patients treated could safely eat the exit dose of one to three peanuts. The study leaders reported their findings in the March 12, 2019 Journal of the American Medical Association.

Still, the patch has worked wonders forsome. In 2012, Sharon Wong was desperate. Her sons allergies to peanuts andtree nuts had intensified to an alarming degree. Once during a shopping trip,he went into a coughing fit while walking past a batch of freshly baked walnutcookies. At a restaurant buffet, he started vomiting after merely looking at asteamy tray of pesto pasta. (Pesto is made with pine nuts.)

It was really awful, recalls Wong. Wecannot control the air he breathes. But we didnt want to keep him confined athome. We wanted him to be able to go shopping, to go down the street, to go tofriends homes and not stress about his allergies.

That year she enrolled her son, then nine years old, in an earlier-stage peanut patch trial in the San Francisco Bay area of California. At first, it took just 1/240th of a peanut to trigger an allergic reaction. After two years on the patch, he could tolerate about six peanuts.

We feel more comfortable about travelinglonger distances and dining in restaurants with precautions in place, Wongwrote in a blog about the patch trial. Each mini-success gives usconfidence and improves our quality of life. My son is happier and healthier.

In August, the FDA plans to review data on the peanut patch and recommend if it should be approved. DBV Technologies is also researching and developing patches to treat milk and egg allergies. And as for oral therapies, Aimmune recently started a new trial for its egg-allergy treatment. The company is also developing an oral therapy for walnut allergy.

Scientists are studying other related approaches, too. One is an immune therapy that uses liquid droplets containing allergens. These are placed under the tongue rather than swallowed directly. Edwin Kim, an allergist at the University of North Carolina School of Medicine, in Chapel Hill, led one study of children treated for three to five years with this sublingual therapy. All had peanut allergies. Of the 37 kids who completed the study, two in every three could now consume 750 milligrams (0.03 ounce) or more of the peanut allergen. Kim, whose center has helped conduct studies for DBV and Aimmune (among other companies), reported the findings last November in the Journal of Allergy and Clinical Immunology.

Additional experimental treatments block other parts of theimmune response to allergens. Some act together with oral therapy, allowingfewer allergic reactions during therapy. Others supply helpful gut microbesthat seem to guard against food allergies. And one company is developing atoothpaste to treat peanut allergy.

In the end, each family must decide whether to seek anemerging treatment or stick with just avoiding exposure to the sensitizingfoods. Treatments require diligence. Theyre not yet widely available. And theydont always work. But if the allergy is unbearable, trying a new treatment mightprove worth the time and risk. Clearly, concludes Stukus, the Ohio doctor, food-allergymanagement is not one-size-fits-all.

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Immunology

Dr. Yancopoulos and Regeneron Working on Coronavirus Treatment – The National Herald

By TNH Staff February 6, 2020

Dr. George D. Yancopoulos, Regeneron President and Chief Scientific Officer, spoke at the St. Demetrios Graduation in Astoria. (Photo: TNH/Kostas Bej)

WASHINGTON, DC The United States has announced that it will work with the drug company Regeneron to develop an effective treatment for the new Chinese coronavirus, using drugs that have been tested to fight the Ebola virus.

Many different therapies are currently being tested for the new coronavirus (2019-nCoV), three of which are at an advanced stage: a drug administered to HIV carriers (Kaletra), a combination of drugs used for the coronavirus MERS (antivirals and immunotherapy) and a U.S. company Gilead antivirus that had been previously tested for Ebola virus.

The partnership between the U.S. government and Regeneron concerns a treatment based on monoclonal antibodies. A public-private partnership, like the one we have with Regeneron since 2014, allows us to respond quickly to new global health threats, said Rick Bright, a U.S. health official.

Monoclonal antibodies are copies of one type of antibody prepared in the laboratory. They are a kind of immunotherapy. They attach to certain proteins of the virus and neutralize its ability to invade human cells.

Regeneron has created the cocktail REGN-EB3, which consists of three monoclonal antibodies and last year significantly improved the survival rate of patients infected with Ebola virus in the Congo. The company has also developed a treatment for Middle Eastern Respiratory Syndrome (MERS).

The convincing results of our experimental treatment for Ebola last year showed Regenerons ability to respond quickly to new outbreaks, explained Greek-American Dr. George Yancopoulos, Regenerons President and chief scientific officer.

The cure for the new coronavirus may eventually include many types of medication.

The coronavirus epidemic is likely to have an impact on U.S. supply chains, but the consequences are unlikely to be disastrous, White House financial adviser Larry Cadlow said in an interview with Fox Business, ANA-MPA reported.

Its not a disaster, Cadlow said, adding that weve had it in the past and I just think the impact is minimal, ANA-MPA reported.

The American-born Dr.Yancopoulos,one of the nations leading scientists and head of one of the largest pharmaceutical companies listed on the New York Stock Exchange, grew up inWoodside, Queens. He was the valedictorian of both theBronx High School of ScienceandColumbia University, and received his MD and PhD degrees in 1987 from Columbia Universitys College of Physicians & Surgeons.Yancopoulosworked in the field of molecular immunology at Columbia University with Dr. Fred Alt, and received the Lucille P. Markey Scholar Award for his efforts. In 1989, he left his academic career and became the founding scientist for Regeneron withLeonard Schleifer. Among his honors,Yancopouloswas awarded Columbia Universitys Stevens Triennial Prize for Research and its University Medal of Excellence for Distinguished Achievement. In 2004, he was elected to the National Academy of Sciences and the American Academy of Arts and Sciences.

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Immunology

Kymera Therapeutics to Present Preclinical Data on its First-in-Class Selective and Potent Oral IRAK4 Degraders in Cutaneous Inflammation – Yahoo…

Company names first inflammation/immunology disease indication: Hidradenitis suppurativa

CAMBRIDGE, Mass., Feb. 5, 2020 /PRNewswire/ --Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, today announced the company will present preclinical data demonstrating that oral daily dosing of its IRAK4 degraders completely suppressed IRAK4 protein expression in skin and immune cells and inhibited cutaneous inflammation. Data support the development of Kymera's degraders for chronic inflammatory and autoimmune diseases, including the company's first named inflammation/immunology disease indication, hidradenitis suppurativa (HS). Research will be presented at the 9th European Hidradenitis Suppurativa Foundation Scientific Conference in Athens, Greece on Feb. 6 at 10:30 AM GMT+2 in the Ilissos room of the Athens Caravel hotel (Abstract #86).

(PRNewsfoto/Kymera Therapeutics LLC)

IRAK4 is a protein known to play a significant role in inflammation mediated by the activation of toll-like receptors (TLRs) and IL-1 receptors (IL-1Rs). While TLR and IL-1R signaling via IRAK4 is involved in the normal immune response, aberrant activation of those pathways is the underlying cause of multiple inflammatory and autoimmune conditions, including HS, atopic dermatitis and rheumatoid arthritis.

"Our latest findings build on the data presented last year at the American College of Rheumatology (ACR) showing the ability of IRAK4 knockdown in skin and spleen to suppress cutaneous inflammation in mice," said Jared Gollob, MD, CMO of Kymera Therapeutics. "Importantly, we have also demonstrated that oral daily administration of an IRAK4 degrader leads to complete knockdown of IRAK4 in skin and immune cells in higher species that is well-tolerated. These findings support development in hidradenitis suppurativa, a chronic inflammatory skin disease where robust IRAK4 inhibition has the potential to block the painful, destructive neutrophilic and lymphocytic inflammation driven by chronic TLR and IL-1R activation."

Last November, at the ACR meeting in Atlanta, Kymera introduced its selective and potent oral IRAK4 degraders, showing in vitro inhibition of cytokine and chemokine induction by TLR agonists and IL-1bthat was superior to IRAK4 kinase inhibitors as well as suppression of neutrophil infiltration and IL-1bproduction in vivo in the mouse MSU air pouch model.

"Inhibition of the TLR/IL-1R pathway with a single oral small molecule targeted against IRAK4 has great potential for the treatment of devastating autoimmune and chronic inflammatory diseases like HS, where inflammation is caused by multiple different IL-1 family cytokines as well as TLR stimulation," said Nello Mainolfi, Founder, Presidentand CEO, Kymera Therapeutics. "It is encouraging to see that we can safely achieve the level of IRAK4 knockdown in relevant tissue necessary to treat a disease like HS which has a high inflammatory burden. We look forward to moving our lead compound into the clinic in healthy volunteers by the end of 2020."

EHSF Study Highlights ABSTRACT #86, "Identification of highly potent and selective Interleukin-1 receptor associated kinase 4 (IRAK4) degraders for the treatment of hidradenitis suppurativa," will be presented byVeronica Campbell, Principal Scientist at Kymera Therapeutics.

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About Kymera TherapeuticsKymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body's innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by Pegasus, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, http://www.kymeratx.com.

About PegasusPegasus is Kymera Therapeutics' proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities, and degradation tools.

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Immunology

3 Important Things to Know About Gilead Sciences’ Q4 Results – The Motley Fool

Gilead Sciences (NASDAQ:GILD) made headlines in recent days after the company announced that it was working with Chinese authorities to test its Ebola drug remdesivir in treating the deadly coronavirus strain that has become an epidemic. But that wasn't the biggest news for Gilead this week.

The big biotech reported its 2019 fourth-quarter and full-year results after the market closed on Tuesday. Here are three important things to know about Gilead's Q4 update.

Image source: Getty Images.

Gilead endured a long stretch where its revenue declined quarter after quarter. That wasn't the case in Q4, though. The company reported Q4 revenue of $5.9 billion, up from $5.8 billion in the prior-year period. This result even topped the consensus Wall Street revenue estimate of $5.71 billion.

Sure, Gilead's hepatitis C virus (HCV) franchise continued to weigh on the company's total revenue. HCV sales fell nearly 19% year over year in the fourth quarter to $630 million. But the quarter-over-quarter decline of only 6.5% wasn't too bad considering what Gilead has experienced in the past.

The biggest bright spot for Gilead yet again was its HIV franchise. HIV sales jumped 12% year over year in Q4 to $4.6 billion, with Biktarvy leading the way with sales of $1.57 billion. Although Descovy was the only other HIV drug in Gilead's lineup to deliver sales growth, the combination of it and Biktarvy were more than enough to offset declining sales for Truvada, Genvoya, and other HIV drugs.

Yescarta didn't pick up much momentum in Q4, though. Sales rose nearly 51% year over year in the fourth quarter to $122 million, but that was only slightly above the $118 million recorded in the third quarter.

While Gilead topped Wall Street's Q4 revenue estimate, it was a different story on the bottom line. The biotech posted adjusted earnings of $1.7 billion, or $1.30 per diluted share. This result was lower than the $1.9 billion, or $1.44 per diluted share, generated in the prior-year period. It was also well below the average analysts' Q4 earnings estimate of $1.67 per share.

Gilead's earnings based on generally accepted accounting principles (GAAP) looked much better, though. The company reported GAAP earnings of $2.7 billion, or $2.12 per share, up significantly from GAAP earnings of only $3 million in the prior-year period. However, this big improvement stemmed mainly from some positive tax effects from accounting moves related to asset transfers and net gains from equity securities.

Analysts probably weren't too bothered by Gilead's big adjusted earnings miss. It's possible that they didn't factor in some of the company's acquisition-related expenses.

Gilead provided what could be described as lackluster full-year 2020 guidance. The company projects product sales to be between $21.8 billion and $22 billion. The midpoint of that range is lower than the $22.1 billion in product sales generated in the full year 2019.

Non-GAAP adjusted earnings per share (EPS) for full-year 2020 are expected to be between $6.05 and $6.45. The midpoint of this range is well below the consensus Wall Street adjusted EPS estimate for 2020 of $7.01.

At first glance, it might also appear that Gilead's adjusted EPS will decline from its full-year 2019 level. However, beginning this year, the company isn't excluding stock-based compensation expense from its non-GAAP figures. On an apples-to-apples basis, Gilead's adjusted EPS outlook for 2020 reflects a year-over-year increase of 2% at the midpoint of the guidance range.

If I had to sum up Gilead's fourth-quarter results in one word, it would probably be "blah." There simply was nothing in the company's update to excite investors.

However, pipelines are more important to the prospects for biotech stocks than past quarterly results. Gilead could generate more excitement later this year if it wins FDA approval for immunology drug filgotinib in treating rheumatoid arthritis (RA). Some analysts think filgotinib could achieve peak annual sales in the ballpark of $6 billion if approved for RA and other targeted immunology indications.

Gilead also ended 2019 with cash, cash equivalents, and marketable debt securities totaling$25.8 billion. That's a big cash stockpile the company could use to bolster its pipeline. The company is also putting its ample cash flow to use in another way that should delight investors -- its dividend. Gilead announced an 8% dividend increase beginning in the first quarter of 2020.

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Immunology

It’s a Gut Reaction – Technology Networks

A new study has revealed how the guts protective mechanisms ramp up significantly with food intake, and at times of the day when mealtimes are anticipated based on regular eating habits.

Researchers from the Walter and Eliza Hall Institute found, in laboratory models, that eating sets off a hormonal chain reaction in the gut.

Eating causes a hormone called VIP to kickstart the activity of immune cells in response to potentially incoming pathogens or bad bacteria. The researchers also found that immunity increased at anticipated mealtimes indicating that maintaining regular eating patterns could be more important than previously thought.

With the rise in conditions associated with chronic inflammation in the gut, such as irritable bowel and Crohns disease, a better understanding of the early protective mechanisms governing gut health could help researchers to develop prevention strategies against unwanted inflammation and disease.

The research, led by Professor Gabrielle Belz and Dr Cyril Seillet from the Walter and Eliza Hall Institute, was published in the journal Nature Immunology.

- Eating activates immune cells in the gut that protect against pathogens and preserve gut health.

- Immunity in the gut also ramps up at regular mealtimes in anticipation of eating and a potentially increased risk of infection.

- Understanding the complex interactions between eating, gut health and inflammation could aid in the development of prevention and treatment strategies for chronic inflammatory diseases.

So how does it work?

When food is consumed nerves in the intestine produce a hormone called vasoactive intestinal peptide (VIP) to switch on a protective response in the gut.

Professor Belz said the team showed, for the first time, that food-induced activation of VIP in preclinical models was vital for a subset of immune cells called ILC3s to mount a protective response in the gut.

Food intake switches on VIP, which plays a critical role in alerting the guts army of ILC3 immune cells. In response, ILC3s secrete interleukin-22 (IL-22), which swings into protective action to defend against pathogens and maintain tissue integrity.

We also showed that a deficiency in VIP limits the production of IL-22, which in turn negatively impacts the immune systems ability to prevent unwanted inflammation, she said.

The researchers used advanced imaging techniques to identify the players integral to protective immunity in the gut. Using a new imaging technique that makes tissue translucent, the researchers were able to capture high-resolution, 3D images of how VIP and ILC3 immune cells interact to protect the gut. Results showed their close proximity which confirmed their interdependence.

The researchers also showed that circadian clock genes could enable the gut to ramp up immunity in anticipation of regular mealtimes.

Dr Seillet said baseline gut immunity fluctuated throughout the day, based on circadian rhythms and an anticipatory response to regular eating patterns.

We saw that gut immunity not only spikes with food intake. It also rises and falls due to inbuilt cellular machinery regulated by the circadian clock gene Bmal1, which appears to activate immune cells when eating is likely, Dr Seillet said.

While more work needs to be done to better understand this anticipatory mechanism, the results are very interesting and could help to explain why disruptions to circadian rhythms and regular eating patterns could increase chronic inflammation in the gut.

Dr Seillet said a detailed knowledge about mechanisms for gut protection and tissue repair could be useful for preventing against early-stage gut inflammation, before full-blown disease occurred.

The next steps of our research include gaining a molecular understanding of what properties of food are responsible for kickstarting the process of protective immunity, he said.

For example, are there certain diets that drive a more protective response than others?

ReferenceThe neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity. Cyril Seillet et al. Nature Immunology volume 21, pages168177(2020),https://doi.org/10.1038/s41590-019-0567-y.

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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Immunology

Kineta Invited to Participate at the BIO CEO & Investor Conference – BioSpace

SEATTLE, Feb. 5, 2020 /PRNewswire/ --Kineta Immuno-Oncology., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, neuroscience and biodefense announced today that Kineta's management team has been invited to participate at the BIO CEO & Investor Conference. Craig W. Philips, President, will provide a corporate overview at the conference which is being held February 10-11 at the Marriott Marquis in New York. Now in its 22nd year, the BIO CEO & Investor Conference is one of the largest independent investor conferences focused on established and emerging publicly traded and select private biotech companies.

Presentation DetailsDate: Tuesday, February 11thTime: 10:00 AM, Eastern TimeLocation: New York Marriott Marquis

Kineta, Inc. is a clinical stage biotechnology company committed to developing disruptive life science technologies that address unmet patient needs. We have leveraged our expertise in innate immunity and immunology to advance a focused pipeline of investigational drugs in oncology, neuroscience and biodefense. We actively collaborate with a broad array of private, government and industry partners to advance our innovative products. For more information on Kineta visit our website, http://www.kinetabio.com, follow us on Twitter at @kinetabio, LinkedIn and Like us on facebook.com/KinetaBio.

NOTICE: This document contains certain forward-looking statements, including without limitation statements regarding Kineta's and its affiliates' plans for pre-clinical and clinical studies, regulatory filings, investor returns and anticipated drug effects in human subjects. You are cautioned that such forward-looking statements are not guarantees of future performance and involve risks and uncertainties inherent in Kineta's and its subsidiaries' businesses which could significantly affect expected results, including without limitation progress of drug development, ability to raise capital to fund drug development, clinical testing and regulatory approval, developments in raw material and personnel costs, and legislative, fiscal, and other regulatory measures. All forward-looking statements are qualified in their entirety by this cautionary statement, and neither Kineta nor its affiliates undertake any obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.

Contact:Jacques Bouchy233729@email4pr.com(206) 378-0400

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Immunology

State-of-the-art cancer care at a university level close to home – Freeport Journal-Standard

Yesterday, Feb. 4, was World Cancer Day, an international call to action established in 2000 at the World Summit Against Cancer for the New Millennium in Paris. The day isnt an attempt to raise awareness of any certain type of cancer, but instead the fight that thousands of people and their health care teams are fighting, every day.

We at the Leonard C. Ferguson Cancer Center at FHN Memorial Hospital in Freeport are proud to be part of that fight. In just the past few years, our talented team of professionals has cared for patients fighting 20 different types of cancer, right here on our Freeport campus.

Our medical oncologist-hematologist Arshad Shaikh, MD, offers our patients treatments that are on the front line of immunology, which gives a patients own immune system the power to fight certain cancer cells.

Our radiation oncology team, led by Bobby Koneru, MD, and Gary Shultz, DO, from the Paramount Oncology Group in Dubuque, provides our patients state-of-the-art treatments usually only available in university hospitals. Volumetric Modulated ARC Therapy (VMAT) also called Smart Arc or RapidArc radiation therapy allows our experts to more precisely target cancer cells for treatment, leaving surrounding healthy tissue unharmed.

Though patients dont usually see him at the center, our team includes surgical oncologist Spyridon Theodorakis, MD, FACS. He served fellowships in surgical oncology at Tulane University in New Orleans and at Roswell Park Memorial Hospital in Buffalo, New York, and has made it possible for breast cancer patients to consult and have reconstruction surgery in the same place as their lumpectomy or mastectomy, right here at FHN.

Our center is more than high-tech, though: From the moment a patient walks in our door, were part of his or her team. Our outstanding staff genuinely cares about our patients, and were honored to take time to get to know them and their needs.

Perhaps most importantly, we understand that being diagnosed with cancer is a big, frightening deal. Thats why we offer a three-day guarantee: Youll have a follow-up appointment within three business days of your referral. In addition, you may contact us, even if you arent a regular FHN patient.

When you are diagnosed with cancer, you want a top-notch team of experts working on your treatment as soon as possible. At the Leonard C. Ferguson Cancer Center at FHN Memorial Hospital in Freeport, youve got just that. Call us at 815-599-7000 to get your team together.

Julie Nampel MSN, RN, is the director of the Leonard C. Ferguson Cancer Center at FHN Memorial Hospital in Freeport.

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State-of-the-art cancer care at a university level close to home - Freeport Journal-Standard

Immunology

Illuminating The Intersection Of Art, Science And Technology – KPBS

An ambitious new exhibition at San Diego Art Institute paired local artists with cutting-edge research scientists to create revelatory works ofart

Photo by Bhavna Mehta

Above: A close up of "Fault Lines," a new installation by Bhavna Mehta at San Diego Art Institute.

Decades of scientific progress will converge with the work of dozens of San Diego artists in a major new group show, "Illumination," at San Diego Art Institute (SDAI) in Balboa Park.

One component of the exhibition paired 16 San Diego artists with local scientists studying in a field of interest to the artist. Scientists like Zbigniew Mikulski from the La Jolla Institute of Immunology, Lu-Lin Jiang from Sanford Burnham Prebys Medical Discovery Institute, Krishna Vadodaria from the Salk Institute, Ben Frable from Scripps Institute of Oceanography and more.

The artists spent time in the lab with their matched scientists, furthering their knowledge of a particular research project and developing a piece of work that reflected the science itself, the interactions with the research or researchers or anything that sprung from the collaboration.

When curator Chi Essary asked San Diego-based paper artist and sculptor Bhavna Mehta to participate and to pitch a topic she'd like to work with, Mehta took a gamble: Pitch something too specific. Mehta, who was stricken with polio as a child, selected contagious diseases of the spinal cord, assuming that the idea was too narrow, and it would be unlikely that the project would find a willing scientist for a pairing. It was a last-ditch effort of steering her work away from something she hadn't yet tackled as an artist: her own spine.

"It was a true dread," she said about making art about her own body. "It's not that I've been avoiding it, it's just that I haven't found the language to do it."

Essary, however, delivered. Mehta visited Dr. Samuel Pfaff at the Salk Institute's Gene Expression Laboratory, which specifically studies motor neurons and diseases of the spinal cord. "I have a real deep personal connection with the Salk Institute," Mehta said. Researchers from the lab also visited Mehta's studio to learn more about her work.

One revelation for Mehta throughout the process was the fundamental intersections of art and science: the value of questions and the pursuit of the unexpected.

"I don't make a lot of art expecting something, because I think you're always disappointed," she said, and felt similarity with the scientists. "You're willing to be surprised by what you find."

Mehta's piece, a massive installation called "Fault Lines," uses hundreds of small paper cut forms and pins to create a cross section of her spinal cord.

The spinal cord is like a superhighway of activity and information, with motor neurons sending messages through the entire body and controlling activity, sensation and what Mehta described as "the involuntary dance of organs." These elements are represented by gray, white, yellow, vivid orange and purple shapes, pinned directly to the wall in 3-dimensional relief. These are the specific tiny things that polio ravages, blown up to 200 times their size.

"It's always going to be painful for me," Mehta said, about the process of creating this piece and understanding her own history. "But the purpose of art is not to show but to discover."

Another impactful pairing in the project was that of scientists Zbigniew Mikulski ("Dr. Z") and Dr. Sara McArdle with filmmaker Cy Kuckenbaker.

"It was very much like giving a little kid a video game joystick for the first time," Kuckenbaker said. With access to one of the La Jolla Institute of Immunology's microscopes over the course of three extended visits to the lab, he began to understand the magnitude of the information stored in each cell in the human body.

Kuckenbaker's project includes a video installation, but strikingly, he also printed out all of the data included in a single chromosome, one of the smallest: chromosome 22. "It took five days to print," he said.

Each page is a combination of base pairs represented by the letters GCAT in sequences for 10,000 pages, or 5,000 sheets of paper. That's just for one chromosome. Each cell contains a whopping 46 of these chromosomes including the copies, and the human body contains trillions of cells. For Kuckenbacker, creating a tangible work of art from these quantifiable but astronomic facts is a way of understanding and relating something unfathomable.

The pages are bound into a book that, when set on the floor, reaches about knee height. For Kuckenbaker, it shows the "extraordinary efficiency in nature."

To round out the show, SDAI invited 10 more local artists to show pieces. These artists all routinely create work that deals with technology, climate, global health or other scientifically relevant themes, including Yasmine Kasem, and Los Angeles-based Young Joon Kwak, who created a bright pink twisted neon sculpture for the exhibition.

The exhibition opens Saturday, Feb. 8 with an opening reception, and runs through May 3 at SDAI in Balboa Park. Admission is free to San Diego Art Institute for the entirety of 2020.

Correction: An earlier version of this story incorrectly identified base pairs. The story has been updated to reflect the change.

KPBS' daily news podcast covering local politics, education, health, environment, the border and more. New episodes are ready weekday mornings so you can listen on your morning commute.

Julia Dixon Evans Arts Calendar Editor and Producer

I write the weekly KPBS Arts newsletter and edit and produce the KPBS Arts calendar. I am interested in getting San Diegans engaged with the diversity of art and culture made by the creative people who live here.

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Illuminating The Intersection Of Art, Science And Technology - KPBS

Immunology

FDA just approved the first treatment for peanut allergies – The Daily Briefing

FDA on Friday approved Aimmune TherapeuticsPalforzia, the first-ever treatment for life-threatening peanut allergies.

Infographic: 6 ways your pharmacist can save the day

Theincidenceof peanut allergies in children in the United States has increased by 21% since 2010, according to theAmerican College of Allergy, Asthma, and Immunology. The latest estimates suggest about 2% to 5% of U.S. children have a peanut allergy.

There's a significant debate among providers about how to prevent or treat peanut allergies. Recent guidelines have recommended parents begin feeding their children peanuts at a young age to help their immune systems learn how to tolerate peanuts.

Researchers and some providers have tested a similar approach, known as oral immunotherapy, on kids who already have developed a peanut allergy. The technique involves slowly introducing children to small amounts of peanutsbut according to The Atlantic, many providers view such experiments as risky.

Palforzia is a capsule that contains small amounts of peanut powder.

For the treatment, doctors prescribe and administer a small dose of the drug, which can be mix with applesauce or another food. After the initial dose, patients must take the drug daily with doctors increasing the dose 11 times over several months until the patient is ingesting the equivalent of about one peanut. Doctors must administer each dosage increase, and if the patient tolerates the increase they may continue that dosage at home.

Researchers employed by Aimmune in 2018 published clinicaltrialresults in theNew England Journal of Medicineshowing that after a one-year period, two-thirds of children taking the treatment could safely consume two peanuts in a controlled setting, compared to 4% of patients who did not take Palforzia, according to the Associated Press.

FDA on Friday approved Palforzia, making it the first drug to receive FDA approval to treat life-threatening peanut allergies. The goal of the treatment is to reduce the risk of a life-threatening allergic reaction, not to make it so that individuals with peanut allergies can regularly eat peanuts. Aimmune CMO Daniel Adelman said Palforzia is only "intended to desensitize patients to peanut protein. So while they still must practice avoidance, it can mitigate allergic reactions after accidental consumption."

The drug is approved for children ages four to 17 who have a confirmed diagnosis of peanut allergy. According to FDA, "Those who take Palforzia must continue to avoid peanuts in their diets."

Researchers assessed the effectiveness of Palforzia in a randomized, double-blind, placebo-controlled study that enrolled about 500 people who were allergic to peanuts. Researchers found 67.2% of participants who took Palforzia recipients tolerated a 600 mg dose of peanut protein after six months, compared to 4.0% of participants who received the placebo.

Researchers assessed safety using two double-blind, placebo-controlled studies in about 700 people with peanut allergies. Researchers found the most common side effects were abdominal pain, nausea vomiting, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis. The risk of anaphylaxis is why FDA required patients to take the initial dose and the increased dosages in the presence of a doctor.

The medication will cost $890 per month, but Aimmune said it will offer an assistance program that will reduce the patient's share of the cost to as low as $20 for some patients.

Some providers said the drug could be a "big deal" for patients who live in constant fear of making contact with peanuts.

Subhadra Siegel, chief of pediatric allergy and immunology at New York Medical College, said, "The thought of relieving that anxiety and being able to eat in a restaurant without worry. These are huge debilitating things for families with food allergies."

Two separate surveys found that allergists favor Palforzia as a treatment for patients with peanut allergies, with analysts predicting the drug will make about $52 million in 2020 and as much as $830 million in 2023.

Given the drug would be the first ever to treat life-threatening peanut allergies, Aimmune projects that Palforzia's annual sales could exceed $1 billion.

However, some experts said the new drug is simply an overpriced version of peanut flour, which can be sold as a dietary supplement at a much lower cost.

A study by the Institute for Clinical and Economic Review found that there was no sufficient evidence that using Palforzia would be more effective than avoiding peanuts or another oral immunotherapy.

But Thomas Casalechief medical adviser atFood Allergy Research & Education(FARE), a nonprofit advocacy and lobbying group that helped create Aimmuneargued that, even though supplement manufacturers can offer cheaper versions of peanut flour, having an FDA-approved version makes the treatment safer and more accessible to patients.

Still setting aside price, the drug raises other concerns.

While researchers in an Aimmune clinical trial found that patients showed greater tolerance of peanuts in a clinical setting, outside of the laboratory they actually experienced more serious allergic events. According to The Atlantic, 14% of those receiving the peanut powder pill reported a severe allergic reaction during the study period, compared with just 3% in the placebo group. Ameta-analysispublished inThe Lancetconfirmed the risk.

Jeff Tice, a physician and health policy analyst at the University of California at San Francisco who examined the product, said, "This is just what we're trying to preventhaving to get taken to the ER sort of outcome." He added, "The trials clearly demonstrated desensitization [to peanuts], but apparently at the cost of more harm, and no clear evidence of long-term benefit" (Hamblin,The Atlantic, 9/13/19; Johnson, Washington Post, 1/31; Loftus, Wall Street Journal, 1/31; FDA release, 1/31; Feurstein, STAT+, 2/3).

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FDA just approved the first treatment for peanut allergies - The Daily Briefing

Immunology

Trinity researchers in potential MS treatment breakthrough – The Irish Times

An important discovery that could lead to more effective treatments for people living with multiple sclerosis (MS) and other autoimmune diseases such as psoriasis and rheumatoid arthritis, has been made by scientists from Trinity College Dublin.

The researchers have identified the role played by a specific immune molecule, known as IL-17, in priming cells that cause the disease. Rather than being directly involved in damaging the nervous system, IL-17 kick-starts the disease-causing immune response that mediates the damage, they believe

Their work, published in Immunity scientific journal, also suggested there is significant potential in drugs that target the IL-17 molecule, both for MS and psoriasis/rheumatoid arthritis.

MS is a debilitating disease that affects some 2.3 million people globally and over 9,000 people in Ireland. It is associated with infiltration of immune cells into the brain and spinal cord that cause damage to nerves, leading to neurological disabilities.

However, the cause and precise immunological basis to this autoimmune disease is still unclear.

Studies in a mouse model of MS, called experimental autoimmune encephalomyelitis (EAE), have shown that immune T cells, which secrete IL-17, cause damage to the myelin sheath that surrounds nerves in the central nervous system (CNS).

Early clinical trials with antibody-based drugs that block IL-17 are showing promise in the treatment of relapsing-remitting MS and have already been licensed for the treatment of psoriasis.

The Irish research outlines a new role for IL-17 in EAE and, potentially, in MS. The new research shows that, instead of playing a direct part in CNS pathology, a key role of IL-17 is to mobilise and activate an army of disease-causing immune cells in the lymph nodes that then migrate to the CNS to cause the nerve damage, said Prof Kingston Mills, professor of experimental immunology at TCD.

Crucially, our findings suggest that drugs that block IL-17 may not need to get across the blood-brain-barrier to be effective in treating MS, add Dr Aoife McGinley, another member of the research team.

So, as well as shedding new light on the importance of IL-17 as a drugs target in RR MS, our research highlights the huge potential of drugs that block IL-17 in the treatment of other autoimmune diseases.

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Trinity researchers in potential MS treatment breakthrough - The Irish Times