Category Archives: Immunology

Immunology

Study reveals factors influencing outcomes in kidney cancer treated with immunotherapy – Science Codex

BOSTON - By analyzing tumors from patients treated with immunotherapy for advanced kidney cancer in three clinical trials, Dana-Farber Cancer Institute scientists have identified several features of the tumors that influence their response to immune checkpoint inhibitor drugs.

The research was presented during the Clinical Science Symposium at the American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in Nature Medicine. The researchers say the study provides important clues about kidney cancer genetics and its interaction with the immune system that may prove to be vital in our ability to predict which patients are likely to benefit from immunotherapy drugs, which have been approved for first- and second-line treatment in the disease, but which don't work in all patients. The study showed that features that are typically linked to immunotherapy response or resistance in other types of cancer don't work the same way in advanced clear cell renal cell cancer (ccRCC).

"Kidney cancer breaks all those rules," said David Braun, MD, PhD, a Dana-Farber kidney cancer specialist and first author of the report. Co-senior authors are Toni Choueiri, MD, Catherine J. Wu, MD, Sachet A. Shukla, PhD, and Sabina Signoretti, MD all of Dana-Farber. Other authors are from the Broad Institute of MIT and Harvard, Bristol Myers Squibb, and Brigham and Women's Hospital.

Clear cell renal cell cancer is the most common form of kidney cancer. There are about 74,000 new cases of kidney cancer in the United States each year, and about 15,000 deaths. Checkpoint inhibitor immunotherapy drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) used in advanced kidney cancer work by blocking PD-1, a protein on immune T cells that normally keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against kidney cancer cells.

PD-1 checkpoint inhibitors have brought a powerful new weapon to bear on advanced kidney cancer, which generally doesn't respond to standard chemotherapy. In cancers such as melanoma and lung cancer, checkpoint inhibitors - drugs like pembrolizumab (Keytruda) and nivolumab (Opdivo) - tend to be more effective against tumors with a "high mutational burden," that is, their DNA is riddled with many mutations. Advanced clear cell renal cell cancer, by contrast, has a moderate number of mutations yet is relatively responsive to checkpoint inhibitors - and scientists don't know why that is. Another puzzling difference is that in melanoma and some other cancers, tumors that are infiltrated with large numbers of immune CD8 T cells, creating what's termed an inflamed or "hot" environment within the tumor, respond better to PD-1 blockade. But the reverse is true in advanced kidney cancer - high infiltration by CD8 T cells is associated with a worse outcome.

In this study, the scientists analyzed 592 tumors collected from patients with advanced kidney cancer who were enrolled in clinical trials of PD-1 blocking drugs. They used whole-exome and RNA sequencing and other methods to uncover the genomic changes and other factors that were associated with how the patients' tumors responded to the drugs - specifically, the patients' progression-free survival and overall survival.

The study was aimed at determining what features of advanced kidney cancer cells were associated with their response or resistance to PD-1 inhibitors. In analyzing the tumors from advanced ccRCC patients treated with PD-1 inhibitors, the investigators looked for biomarkers - genetic changes, mutations, copy number alterations, and so forth - in the genomes of the kidney cancer cells that might be correlated with patient outcomes - such as progression-free survival and overall survival.

Braun said that some of the most interesting findings were characteristics of the kidney tumors that - unlike with other types of cancer - did not influence responsiveness to PD-1 inhibitor drugs. For example, tumors containing a large number of neoantigens - proteins made by cancer-related DNA mutations that may make the tumors more responsive to immunotherapy, but this proved not to be true of the kidney tumors. Also, even though the kidney tumors were heavily infiltrated by CD8 immune T cells - which causes other kinds of cancer to provoke a strong immune attack against the tumors - this actually led to no difference in outcome for these kidney cancer patients. "To our surprise, the immunologically 'hot' tumors did not respond any better than the 'cold' tumors," said Braun.

Another factor that affects responsiveness in some types of cancer - the specific HLA molecules inherited by individuals that present antigens to the immune system - didn't affect the immune response to advanced kidney tumors. "That surprised us," said Dr. Wu, chief of Division of Stem Cell Transplantation and Cellular Therapies. "We reasonably hypothesized that the potential of the patient's immune system to present and react to a greater diversity of antigens may be associated with better outcomes, but clearly kidney cancer does not fit the standard mold," noted Wu.

"However, we did uncover some factors that may explain the unexpected observations," said Dr. Shukla who leads the computational group at the Dana-Farber Translational Immunogenomics Laboratory. The study uncovered that advanced kidney tumors heavily infiltrated with CD8 T cells did not respond well to immune checkpoint blockers even though they were immunologically "hot" tumors. The scientists, with their comprehensive analysis of changes in the kidney tumors' genomes, found that the tumors were depleted of mutated PBRM1 genes - which are correlated with improved survival with PD-1 blockade therapy - and also had an abundance of deletions of a chromosomal segment known as 9p21.3, which is associated with worse outcomes with PD-1 blockade. "We believe that these two factors may explain why CD8 T cell infiltration of the tumors did not make them responsive to checkpoint blocker therapy," explained Shukla, "while other types of cancer that exhibited CD8 T cell infiltration but did not have those chromosomal changes did respond."

"Our work highlights the importance of integrating genomic data with immunopathologic data generated through painstaking review by expert pathologists," said Dr. Signoretti, professor of pathology at Harvard Medical School. "Our findings reveal that interactions between immune T cell infiltration and alterations in the tumor DNA (such as inactivation of the PBRM1 gene and the abundance of 9p21.3 deletions) can be important influences on tumors' response to PD-1 blockade - perhaps not only in kidney cancer but in other types of tumors as well."

"The current study provides critical insights into immunogenomic mechanisms contributing to response and resistance to immunotherapy in clear cell renal cell cancer," said Dr. Choueiri, director of the Lank Center for Genitourinary Oncology and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. "The detailed clinical, genomic, transcriptomic, and immunopathology data produced by this study will serve as a valuable resource for the cancer immunology community. This work, therefore, will be important for ongoing research in precision medicine and immuno-oncology, helping to identify which patients are likely to respond to current therapies, and providing fundamental information to aid in development of rational combination therapies to overcome resistance in the future."

"One notable thing," said Choueiri, "is the collaboration between multiple disciplines and stakeholders: Immunology, pathology, genetics, computational and clinical expertise all converged on one tumor, while involving academic and industry stakeholders."

See original here:
Study reveals factors influencing outcomes in kidney cancer treated with immunotherapy - Science Codex

Immunology

Learning how the coronavirus affects the body offers clues to fight COVID-19 – CBC.ca

This is an excerpt fromSecond Opinion, aweeklyroundup of eclectic and under-the-radar health and medical science news emailed to subscribers every Saturday morning.If you haven't subscribed yet, you can do that byclicking here.

The devastating damage that the novel coronavirus inflicts on the human body can set off inflammatory havoc. As we learn more, doctors are gaining clues to hopefully prevent deaths and improve treatment.

Last December, COVID-19 entered the world stage as a flu-like illness causing fever, dry cough and a sore throat.

Since then, the list of how the illness can present has expanded, and expanded again, to include gastrointestinal symptoms like diarrhea, general aches, loss of taste and smell and serious blood-clotting problems, among others.

Of the more than five million infections globally so far, 2.4 million have recovered.

Most infected people have so few symptoms they are better off at home. The minority of serious infections in patients mainly those over 65, though no age group is left unscathed can confound health professionals caring for them.

The illness can worsen to a severe stage called Acute Respiratory Distress Syndrome, which includes severe lung inflammation and damage. These are often the patients who are admitted to intensive care units and need life support such as ventilation.

Dr. Lynora Saxinger, an infectious disease physician at the University of Alberta, co-chairs a provincial scientific advisory board reviewing how COVID-19 manifests and what it means for reducing transmission and extending treatment beyond current care measures.

"The landscape shifts really quickly," Saxinger said. "We just want to make sure that we're not missing [what] could be spreading, because that's where we're going to run into trouble."

As initial anecdotes about inflammatory-like effects such as blood-clotting complications mounted into a clearer signal for caution, clinicians adapted their care while scientists worked to understand why it happens.

Now, Saxinger said there's more evidence of clotting damage in both large and small blood vessels."This virus is doing different things in the body."

Experts say some of these inflammatory effects look to be unique to this particular coronavirus, which is known asSARS CoV-2.

Dr. Zain Chagla, an associate professor of infectious disease at McMaster University in Hamilton, Ont., said the wide extent of clotting with this virusdiffers from other infections, including from the deadly SARS and MERS coronaviruses.WithCOVID-19, the clots occur in veins in the legs and lungs, as well as in arterial ones that cause strokes and can lead surgeons to resort to amputating a patient's limbs.

Medical researchers have also found tiny clots that damaged tissue throughout the body in hospitalized patients and in autopsies.

Chagla said this means that "from a therapeutic standpoint," it might be better to give patients a low dose of heparin,an anticoagulant or blood thinner. It's often used before surgery and in a variety of medical conditions to prevent and treat clots.

Clinical trial researchers are also exploring the use of high-dose anti-coagulants in carefully selected patients, Chagla said.

This week, Health Minister Patty Hajdu announced an accelerated path for clinical trials to help find answers to urgent COVID-19 diagnosis, treatment, mitigation or prevention questions while keeping patients safe.

On Friday, Montserrat Puig of the U.S. Food and Drug Administration and her team published what they called a road map for effective treatment of COVID-19, based on both repurposing existing approved drugs as well as those still under development.

The review, published in Frontiers in Immunology, unravels factors leading to the "cytokine storm" that can rampage in people with severe COVID-19. Cytokines are small molecules released by the body's immune system to co-ordinate response against an infection or injury, ranging from a mild fever to suspected deaths in the 1918 flu pandemic.

Scientists are still working to understand the key events in cells, tissues and the body's immune system that tips the balance from a normal, protective, "hey, come help" call for reinforcements to an unnecessary, four-alarmcall that leads to a life-threatening overreaction.

Puig wrote that potential drugs include those that could block the virus from entering our cells in the first place, antivirals to stop the virus from making copies of itselfand therapies called monoclonal antibodies that dampen the haywire response from cytokines.

People who develop symptoms of COVID-19 do so within 14 days, and it mostly occurs about five days after exposure.

Saxinger said when patients struggle with congested lungs and poor blood pressure control, it's often a manifestation of lung inflammation in response to the infection.

She said there's also an arc to the story of how the disease marches through the body from initial infection to damage to recovery or death.

"The initial infection triggersthis body-wide response that is devastating," Saxinger said. "Then, when the infection itself might be coming under control, it's almost like you unleash this storm of immune reactivity and inflammation."

Once the storm is set off, doctors say treating the infection itself is unlikely to help much.

So, what could help? As physicians report more symptoms, scientists working in parallel are exploring why and how the virus replicates in some tissues and organs so well.

Matthew Miller, an associate professor of infectious disease and immunology at McMaster, is following the scientific advances.

The virus seems to use a receptor called ACE2 to enter human cells. Miller said many groups of researchers are working to understand what cells in our body have active proteins where the virus might be able to replicate and cause disease.

"Knowing what cells a virus is capable of infecting is really important, because it can help us anticipate what types of diseases or what types of symptoms it might cause," Miller said.

It's thought that the infectious dose a person is exposed to,as well as minute, genetic differences in the individual and whether theyhave underlying health conditions (like heart disease or diabetes)all play a role in how COVID-19 manifests.

For now, medical researchers are exploring how ramping up a beneficial aspect of the immune response that cells normally use to kill off a virus could be complemented with "immune modulators" to tamp down overreactions. It's a delicate balance and timing is key.

Miller said as we learn more about the unique features of SARS-CoV-2, governments and public health officials have been forced to "learn on the fly" and adapt pandemic plans built for a different respiratory infection:influenza, commonly called flu.

"One of the areas that this pandemic has really brought to light is that there's not enough focus on prevention control measures," he said.

Countries imposed and eased lockdowns without a firm grasp on what measures work best for this particular virus, leading to differences across the globe and shifting recommendations on wearing masks or physical distancing.

"I think we're all learning that we don't understand nearly as well as we should," Miller said.

WATCH | Why we should expect waves of COVID-19:

Public health basics like staying home when sick, handwashing and cough etiquette apply to all respiratory pathogens. It's the specifics that are still a work in progress.

For Saxinger, these knowledge gaps mean that understanding COVID-19 will be a long-term effort.

"It's not just going to be a one, we're done," Saxinger said. "We are all going to have to figure out the best way to manage people and try to give them the best outcomes possible."

To read the entireSecond Opinionnewsletter every Saturday morning, subscribe byclicking here.

Link:
Learning how the coronavirus affects the body offers clues to fight COVID-19 - CBC.ca

Immunology

OU College of Medicine > Academic Departments > Internal …

There are 12 clinical and research Faculty in the Rheumatology, Immunology and Allergy Section (RIA) University of Oklahoma and Oklahoma Medical Research Foundation combined research program. Please access the OMRF web sitehereto find a description of their research interests and recent publications.

The research program of the Rheumatology, Immunology and Allergy Section(RIA) of the Department of Medicine at the University of Oklahoma Health Sciences Center (OUHSC) is integrated with the Arthritis and Clinical Immunology Research Program at theOklahoma Medical Research Foundation(OMRF). Research faculty is assigned research space at both the Oklahoma Medical Research Foundation and the University of Oklahoma Health Sciences Center.

Most of the work underway is unified under autoimmunity or inflammation. Systemic lupus erythematosus is a particular focus of many of the faculty. Our investigators lead large, multi-investigator projects such as Centers of Biomedical Research Excellence in Immunology and Autoimmunity, the Oklahoma Rheumatic Disease Research Cores Center, Autoimmunity Center of Excellence and Center of Research Translation in Sjogrens syndrome. We house a number of large patient collections in diseases such as systemic lupus erythematosus, Sjgrens syndrome, rheumatoid arthritis and related disorders. In addition, the faculty has available a CLIA approved laboratory for the serologic diagnosis of lupus and other autoimmune rheumatic disease syndromes.

Excerpt from:
OU College of Medicine > Academic Departments > Internal ...

Immunology

Dr. Amir Bajoghli’s Article on Shiitake Mushroom Dermatitis Featured in Premier Immunology Publication – Yahoo Finance

MCLEAN, VA / ACCESSWIRE / May 29, 2020 / The shiitake is an edible mushroom native to East Asia. The popularity of these mushrooms has increased over the years in the United States and with it has been a rise in allergic skin reactions to this relatively new ingredient on the American culinary landscape.

Shiitake flagellate dermatitis, also known as toxicoderma, is an allergic reaction related to the ingestion of raw or undercooked shiitake mushrooms. Signs of this dermatologic condition include skin eruptions resembling scratch or whiplash marks. This skin reaction occurs in approximately 2-3% of people who eat undercooked or raw shiitake mushrooms.

Various theories exist as to how and why this type reaction occurs with some people who eat the undercooked forms of the edible fungus.

When Dr. Amir Bajoghli of Skin & Laser Dermatology Center recently treated such a case in his practice, he realized it was of importance to share his medical findings regarding the patient with the scientific community. He wrote up the details of this Shiitake mushroom dermatitis. These findings were published in the Annals of Allergy, Asthma & Immunology, the premier publication for allergic and immunologic diseases.

Dr. Bajoghli is honored to publish the case with his father, Dr. Mehdi Bajoghli, a practicing allergist in Northern Virginia.

Dr. Amir Bajoghli has been active in the practice of dermatology and laser surgery since the completion of his training at the combined Tufts University and Boston University. He regularly presents lectures to other physicians regionally and internationally, and teaches medical students and dermatology residents at Georgetown University.

Dr. Amir Bajoghli can be reached at either of his Virginia offices:

McLean:1359 Beverly Rd., 2nd FloorMcLean, VA 22101(703) 893-1114

Woodbridge:2200 Opitz Blvd., Suite 100Woodbridge, VA 22191(703) 492-4140

SOURCE: Skin and Laser Dermatology Center

View source version on accesswire.com: https://www.accesswire.com/591993/Dr-Amir-Bajoghlis-Article-on-Shiitake-Mushroom-Dermatitis-Featured-in-Premier-Immunology-Publication

Excerpt from:
Dr. Amir Bajoghli's Article on Shiitake Mushroom Dermatitis Featured in Premier Immunology Publication - Yahoo Finance

Immunology

Burnham recognized by national microbiology society – Washington University School of Medicine in St. Louis

Visit the News Hub

Honored for research and leadership in clinical microbiology

Burnham

Carey-Ann D. Burnham, PhD, a professor of pathology and immunology at Washington University School of Medicine in St. Louis, has received the Award for Research and Leadership in Clinical Microbiology from the American Society for Microbiology. The award recognizes an outstanding scientist and clinical microbiologist with distinguished research achievements and a record of innovation who has advanced the profession of clinical microbiology.

Also a professor of medicine, of molecular microbiology and of pediatrics, Burnhams research focuses on antimicrobial resistance. She is particularly interested in how multidrug-resistant organisms arise and spread, especially within hospitals, and in developing novel diagnostic methods for detecting drug-resistant strains of bacteria such as Staphylococcus aureus and Clostridium difficile.

Burnham is the medical director of clinical microbiology at Barnes-Jewish Hospital, as well as the program director for the universitys postdoctoral fellowship training program in medical and public health microbiology, and the vice chair of faculty mentoring and advancement in the Department of Pathology & Immunology. Currently, she is part of the leadership team developing diagnostic and antibody tests for COVID-19.

See the article here:
Burnham recognized by national microbiology society - Washington University School of Medicine in St. Louis

Immunology

Researchers review all clinical and research findings related to COVID-19 – News-Medical.Net

Due to the devastating worldwide impact of COVID-19, the illness caused by the SARS-CoV-2 virus, there have been unprecedented efforts by clinicians and researchers from around the world to quickly develop safe and effective treatments and vaccines.

Given that COVID-19 is a complex new disease with no existing vaccine or specific treatment, much effort is being made to investigate the repurposing of approved and available drugs, as well as those under development.

In Frontiers in Immunology, a team of researchers from the U.S. Food and Drug Administration reviews all of the COVID-19 clinical and research findings to date.

They provide a breakdown of key immunological factors underlying the clinical stages of COVID-19 illness that could potentially be targeted by existing therapeutic drugs.

Dr. Montserrat Puig of the U.S. Food and Drug Administration, the senior author of the review, stated that "there are multiple factors involved in determining if the patient's immune response will be insufficient or successful in combating the infection."

"Our review is an overview of these factors and how they can be considered to define the context in which medications currently used for other diseases, or development of novel agents, can be utilized to prevent, ameliorate or cure COVID-19."

We know that during the early stage of COVID-19 people can show no symptoms or mild symptoms, and for many, the disease resolves.

For others, it can be catastrophic. The illness can progress to a severe stage with manifestations including Acute Respiratory Distress Syndrome, accompanied by severe lung inflammation and damage.

Patients with severe COVID-19 are often admitted to intensive care units and require life support with medical ventilation.

This review compiles and summarizes published up-to-date studies unraveling the factors leading to the cytokine storm and its consequences observed in COVID-19, including the immunological events underlying the severe manifestation of the disease.

The analysis is further supplemented with knowledge previously acquired from other coronaviruses including SARS-CoV and MERS-CoV.

The authors underscore key immunological events that might tip the balance from a protective to a hyperinflammatory response leading to life-threatening conditions.

They outline a promising list of currently available drugs that are either understudy or under consideration for use in COVID-19 based on their potential to influence these key immunological events.

These drugs include those that could inhibit SARS-CoV-2 entry into host cells, antivirals with the potential to block SARS-CoV-2 replication or factors that could boost the antiviral response, monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response and therapeutics that could improve the function of the lungs.

Puig states that "approaches to therapy in the early stage of the disease will differ from those in its severe late stage."

Adding that "as the results of clinical trials become available, it may become increasingly clear that there is likely no single magic bullet to resolve the disease but a combination of several interventions that target different key factors of COVID-19 may well be required."

Puig cautions that "the research and data obtained from COVID-19 studies are rapidly evolving and continuously updated. Thus, as clearly stated in our review, the information provided is a 'lessons learned' to date and describes the knowledge available at the time of the publication of the review."

The description of the immunological profile of the clinical stages of COVID-19 provided in this review will enable more informed decisions about the type and timing of treatments to be evaluated in clinical trials.

Our hope is that the information contained in our review will help professionals in COVID-19 research develop new tools and agents to better treat those at high risk of severe COVID-19."

Dr. Montserrat Puig, Study Senior Author, U.S. Food and Drug Administration

Source:

Journal reference:

Cardone, M., et al. (2020) Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation. Frontiers in Immunology. doi.org/10.3389/fimmu.2020.01131.

Read more from the original source:
Researchers review all clinical and research findings related to COVID-19 - News-Medical.Net

Immunology

CSU cancer researcher named 2020 Boettcher Investigator – Source

Dan Regan, an assistant professor in Microbiology, Immunology, and Pathology, was recently selected to receive the Boettcher Foundations 2020 Webb-Waring Biomedical Research Award.

The award supports promising early-career scientific investigators, allowing them to establish their independent research and make it competitive for major federal and private grants.Recipients, known as Boettcher Investigators, are awarded $235,000 to sustain up to three years of biomedical research. Regan joins seven other recipients from five of Colorados top research institutions and is the 12th scientist at Colorado State University to receive the award.

I am grateful to the Boettcher Foundation for their commitment to biomedical research, said Regan. This award provides a fantastic opportunity to gain momentum and make an impact in my field.

This class of Boettcher Investigators are the example of Colorados innovation in bioscience research that aims to improve our preparation, response, and deepen our knowledge of human health issues, said Katie Kramer, president, and CEO of the Boettcher Foundation. We are proud to support their expert work at this significant juncture in their research careers.

Regans work in metastatic cancer research at his Investigational Pathology Lab at the Flint Animal Cancer Center caught the attention of the Boettcher Foundation.

Many types of cancer, in both pets and people, spread to the lungs, Regan said. Once cancer progresses, we have few treatment options. My work focuses on looking at tumor metastasis through the lens of the tumor microenvironment.

Regan has spent the last decade examining the tumor microenvironment and why some sites in the body promote tumor growth. He explains his work with a simple analogy known as the seed and soil theory. He wants to understand how cancer cells (seeds) know where to find welcoming locations to take root (soil).

With the Boettcher Investigator award, Regan is taking a new approach to his study of metastatic disease. In a unique application, Regan is looking at cells retrieved from the lungs using a diagnostic procedure called bronchoalveolar lavage. The technique uses fluid to wash the lungs and extracts the fluid for examination. Regan has reason to believe certain types of recovered cells have the potential to signal an early warning of tumor metastasis.

Todays imaging technology, such as CT scans, detects tumors, but it can be too late, he said. Biopsies are very invasive. Using this procedure, if we can find earlier clues, we can better guide treatment and hopefully improve patient outcomes.

Building on his preliminary work, Regan plans to spend the next several months gathering additional data from donated human cells and mouse models. The goal is to identify which cell type offers the best signature for early detection.

In addition to laboratory study, the award supports a small clinical trial in dogs with Osteosarcoma, a disease in which 80% of patients experience lung metastasis. Regan will focus on patients who do not appear to have pulmonary tumors based on imaging. Using bronchoalveolar lavage, he will collect patient samples to look for red flags in the retrieved cells. He expects the trial to start sometime next year.

I am grateful to the Boettcher Foundation for their support and taking a chance on a higher risk concept that I believe has the power to pay real dividends for pet and human health, Regan said.

Continue reading here:
CSU cancer researcher named 2020 Boettcher Investigator - Source

Immunology

Dispersed across globe, Brown community finds connection through ‘Dank Stash of Memes’ – The Brown Daily Herald

Richard Bungiro PhD99, senior lecturer in molecular microbiology and immunology, structures his course BIOL 0530: Principles of Immunology around pop culture themes. He challenges students to untangle the hypothetical immunological functions of a Terminator or a dragon. He has an antibody tattooed on his wrist. And he makes memes, which he posts on a Facebook page frequented by hundreds of his current and former students.

Whats your favorite administrative euphemism for global pandemic? Bungiro asked in one of his recent posts. These trying times. These difficult times. These uncertain times. These challenging times. Protect the endowment at all times.

He posted the meme to Brown Dank Stash of Memes for S/NC Teens, a Facebook page where over 20,000 members upload and interact with Brown-related meme content. Over the past four years, the page has become a cultural touchstone for students at Brown. Now, with campus closed as a result of the COVID-19 pandemic, the meme page has helped recreate community for students isolated in their homes. The memes themselves have become a form of communication, of transmitting meaning, that is uniquely suited to the digital existence the Brown community has adopted.

I think people really want to feel like theyre part of a community, Bungiro said. Being on that page and some of the other ones, I think its a way for people to retain a little piece of what were all missing so much right now.

Memes emerged as a cultural phenomenon in the early 2000s, taking the internet and college campuses alike by storm. The word meme was coined to describe elements of culture that propagate through society, particularly through imitation, and are stuck easily to humorous images created and shared through the internet.

Right now this is one of the only public forums that Brown students have as a community, said Lucy Duda 20, a senior administrator of the page as well as a moderator of The Ivy League Meme Consortium, a similar Facebook page with over 100,000 members focused on Ivy League content. Weve really tried to make the meme page a space for public discourse in the community and a way for people to find common ground and bond over how terrible a lot of things have been.

Duda became a moderator of Browns meme page in the fall of 2016, when the page only had a few hundred members. She has seen it grow ever since. In honor of the page hitting 20,000 members, Duda recently made a new cover photo reading Brown Digital Space Main Green.

Throughout the quarantine, memes have poked fun at decisions from the University administration and questioned, often sarcastically, whether students will return to campus this fall. There has also been an influx of more comical content, such as a group of cel-shaded bears dancing to Smash Mouth. Beneath those boogying bears and agitated students lie hundreds of comments of friends tagging each other and reaching out, despite distance and uncertainty, hoping to make each other laugh.

The undertone is very much that things suck, but we can do this, said Elliott Lehrer 21, who has posted memes since he was accepted to Brown three years ago.

Hannah Kierszenbaum 20, who spent her senior spring on College Hill with a few friends, said the meme page has helped keep her connected to the greater Brown community. I relate to it and look at it more now that were in quarantine, she said. It is a subpar situation for everybody so its cathartic to know that other people are also struggling.

These memes will endure beyond the pandemic. Researchers at the University are archiving them at the request of the administrative team behind Brown Dank Stash of Memes for S/NC Teens. Nationally, the Library of Congress is doing the same for other meme content.

John Fenn, contributor to the Library of Congress web archive and head of research and programs at the American Folklife Center, emphasized the communal power of this form of communication, which he defines as narrative, visual communication, contemporary humor that arises out of a collective sense of something, even if its not a collective experience.

Its a fascinating kind of archaeology, Fenn said. Its the archeology of right now.

Andrew Majcher, head of digital services and records management in the John Hay Library, agreed with Fenn.

Especially with the way the COVID crisis has been going, its one of the more poignant ways we can gauge how the student body is feeling about whats going on, Majcher said.

Majcher added that the meme page, along with other pages like Poems from a University Quarantine, might be included in a future University library project on digital documentation of the pandemic.

The lasting impact of the meme page has come as a surprise for Dylan Garcia 20, who co-founded the meme group four years ago.

At the beginning, I thought it was just going to be general memes, Garcia said, who thought that around 2,000 members would join, one-tenth of its current following. He didnt know that the page would end up putting a voice on some issues.

The typical end of the year atop College Hill is Spring Weekend, packed libraries, finals and a stately procession through the Van Wickle Gates. Not this year; no crowded moshes, no late nights in the Rock and Commencement was a half-hour online. Bungiro captured that transition and his feelings toward the community in a meme, composed of a photo of the gates above a photo of his orange couch at home.

Not much snark or spicy in this meme, my friends just sincere gratitude for the students of Brown, the caption reads. You matter, and you constantly remind me why it matters.

Go here to see the original:
Dispersed across globe, Brown community finds connection through 'Dank Stash of Memes' - The Brown Daily Herald

Immunology

Kiniksa Announces Upcoming Presentation on Mavrilimumab in COVID-19 Pneumonia and Hyperinflammation at the European E-Congress of Rheumatology 2020 -…

HAMILTON, Bermuda, May 29, 2020 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (KNSA) (Kiniksa), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today announced an upcoming presentation, entitled Mavrilimumab Improves Outcomes in Severe COVID-19 Pneumonia and Systemic Hyper-Inflammation, showing data from the open-label treatment protocol with mavrilimumab, an investigational fully-human monoclonal antibody that targets granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFR), in patients with severe coronavirus 2019 (COVID-19) pneumonia and hyperinflammation will be delivered at the European E-Congress of Rheumatology (EULAR) 2020. Additionally, preclinical data analyzing the role of the granulocyte macrophage colony stimulating factor (GM-CSF) pathway in giant cell arteritis (GCA) pathophysiology will be included in a poster presentation.

ProfessorLorenzo Dagna, MD, FACP, Head, Unit of Immunology, Rheumatology,Allergy and Rare Diseases IRCCS San Raffaele Scientific Institute andVita-Salute San Raffaele UniversityinMilan, Italywill deliver an oral presentation of outcomes data from the mavrilimumab treatment protocol in COVID-19 pneumonia and hyperinflammation in Italy.

Oral Presentation Details:

There will also be a presentation of preclinical data analyzing the role of the GM-CSF pathway in GCA pathophysiology delivered by Dr.Maria C. Cid, MD, Hospital Clnic,University ofBarcelona, Institut dInvestigacions BiomdiquesAugust Pii Sunyer (IDIBAPS), Vasculitis Research Unit,Department of Autoimmune Diseases,Barcelona,Spain.

Poster Presentation Details:

Kiniksa intends to make the presentations available through the Science section of Kiniksas website (www.kiniksa.com) after the EULAR embargo lifts, which is expected to be at the time of each presentation.

1IRCCS San Raffaele Scientific Institute, Milan, Italy; 2Vita-Salute San Raffaele University, Milano, Italy; 3Kiniksa Pharmaceuticals, Lexington, United States of America; 4Vasculitis Research Unit, Hospital Clinic, University of Barcelona, IDIBAPS.

About MavrilimumabMavrilimumab is an investigational fully-human monoclonal antibody that is designed to antagonize granulocyte macrophage colony stimulating factor (GM-CSF) signaling by binding to the alpha subunit of the GM-CSF receptor. Kiniksas lead indication for mavrilimumab is giant cell arteritis (GCA), an inflammatory disease of medium-to-large arteries. Mavrilimumab was dosed in over 550 patients with rheumatoid arthritis through Phase 2b clinical studies in Europe and achieved prospectively-defined primary endpoints of efficacy and safety. Additionally, Kiniksa and Kite have a clinical collaboration to evaluate mavrilimumab in combination with Yescarta (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma.

About the Mavrilimumab Treatment Protocol in COVID-19 Pneumonia & Hyperinflammation in ItalyThe mavrilimumab open-label treatment protocol was a prospective, interventional, single-active-arm, single-center pilot experience inItaly conducted by Professor Lorenzo Dagna, MD, FACP, Head, Unit of Immunology, Rheumatology, Allergy and Rare Diseases IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University in Milan, Italy within a COVID-19 Program directed by Professor Alberto Zangrillo, Head of Department of Anesthesia and Intensive Care of the Scientific Institute San Raffaele Hospital and Universit Vita-Salute San Raffaele in Milan, Italy. Patients suffering from severe pulmonary involvement of COVID-19, acute respiratory distress, fever, and clinical and biological markers ofsystemic hyperinflammation status were treated with a single intravenous dose of mavrilimumab. The objective of the treatment protocol was to determine whether mavrilimumab in addition to standard management could improve clinical outcomes in patients with COVID-19 pneumonia and hyperinflammation. A control-group was assembled consisting of contemporaneous patients receiving local standard of care and matched for age, sex, comorbidities, baseline inflammatory markers and respiratory dysfunction. Per standard of care of the hospital, all patients received on admission medical treatment with hydroxychloroquine, azithromycin, and lopinavir/ritonavir as well as respiratory support with supplemental oxygen and/or non-invasive ventilation with continuous positive airway pressure.

Story continues

About KiniksaKiniksa is a biopharmaceutical company focused on discovering, acquiring, developing, and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksas clinical-stage product candidates, rilonacept, mavrilimumab, vixarelimab and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions, and offer the potential for differentiation. These pipeline assets are designed to modulate immunological signaling pathways that are implicated across a spectrum of diseases. For more information, please visit http://www.kiniksa.com.

Every Second Counts!

Kiniksa Investor and Media ContactMark Ragosa(781) 430-8289mragosa@kiniksa.com

Read the original:
Kiniksa Announces Upcoming Presentation on Mavrilimumab in COVID-19 Pneumonia and Hyperinflammation at the European E-Congress of Rheumatology 2020 -...

Immunology

RAPT Therapeutics Announces Poster Presentation at the American Society of Clinical Oncology Virtual Scientific Program – GlobeNewswire

SOUTH SAN FRANCISCO, Calif., May 29, 2020 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical companyfocused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, today announced the presentation of a Trials in Progress poster for the ongoing seamless Phase 1/2 clinical trial of FLX475, a small molecule CCR4 antagonist in development for multiple tumor types. The poster was presented at the American Society of Clinical Oncology (ASCO) 2020.

The poster presentation detailed previously reported initial Phase 1 healthy volunteer data for FLX475 that demonstrated excellent safety, pharmacokinetics (PK) and target engagement. FLX475 is designed to block regulatory T cells from migrating to tumor sites, where they suppress immune system responses to cancer cells, without depleting regulatory T cells in the rest of the body nor immune cells required for an anti-tumor response. A robust pharmacodynamic (PD) assay measuring receptor occupancy on circulating regulatory T cells demonstrated that FLX475 achieved exposure levels over the targeted 75%, predicting maximal inhibition of regulatory T cell recruitment into tumors via CCR4 signaling. In addition, levels of FLX475 increased in a dose-proportional manner, with a strong PK/PD correlation observed between drug levels and receptor occupancy.

Building on these data, RAPT initiated a seamless Phase 1/2 study of FLX475. The Phase 1 portion of the trial was a standard dose escalation study in patients with many types of cancer, and the Phase 2 portion is evaluating FLX475 both as monotherapy and in combination with a checkpoint inhibitor in patients with charged tumors, which are tumors that express high levels of CCR4 ligands (CCL17 and CCL22), and have a high presence of regulatory T cells and CD8+ effector T cells. RAPT is currently enrolling the Phase 2 portion of the trial in patients with charged tumors, including non-small cell lung cancer, triple negative breast cancer, head and neck squamous cell carcinoma, cervical cancer as well as EBV-positive nasopharyngeal cancer and lymphomas.

We are pleased with our continued progress in clinical evaluation of FLX475 and remain encouraged by our early observations, said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. The previously reported checkpoint inhibitor-refractory patient with non-small cell lung cancer with a confirmed partial response in the Phase 1 part of this study continues to respond to FLX475 plus Keytruda, and is approaching the 1-year mark of study treatment. Our sites in the U.S., Australia and Asia continue to enroll patients and we remain on track to report results for both the Phase 1 and initial Phase 2 expansion cohorts in the second half of 2020.

The poster presented at ASCO can be viewed on the RAPT website under the Events and Presentation tab of the Investor Relations section here.

About FLX475FLX475 is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Tregrepresent a dominant pathway for downregulating the immune response, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. RAPT is developing FLX475 for the treatment of a broad range of charged tumors, which represent cancer types the company believes are most likely to respond to FLX475, where a large quantity of Tregcells are likely to be the cause of immune suppression within the tumor. FLX475 blocks the migration of Tregto the tumor, which may restore naturally occurring antitumor immunity and synergizing with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators and adoptive T cell therapy.

AboutRAPT Therapeutics, Inc.RAPT Therapeutics is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing its proprietary discovery and development engine, the Company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, FLX475 and RPT193, each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of cancer and inflammation, respectively. The Company is also pursuing a range of targets, including hematopoietic progenitor kinase 1 (HPK1) and general control nonderepressible 2 (GCN2), that are in the discovery stage of development.

Forward-Looking StatementsThis press release contains forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future performances or achievements expressed or implied by the forward-looking statements. Each of these statements is based only on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties. Forward-looking statements include, but are not limited to, statements about the clinical development of FLX475, the interpretation of preliminary observations from the Phase 1 cohort in FLX475 and the continued progress and timing of results from clinical trials of FLX475. Detailed information regarding risk factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in RAPTs Form 10-Q filed with the Securities and Exchange Commission on May 14, 2020 and subsequent filings made by RAPT with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. RAPT disclaims any obligation to update these forward-looking statements.

RAPT Media Contact:Angela Bittingmedia@rapt.com(925) 202-6211

RAPT Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

Read the original here:
RAPT Therapeutics Announces Poster Presentation at the American Society of Clinical Oncology Virtual Scientific Program - GlobeNewswire