Category Archives: Immunology

Immunology

Griffith and Nanostring launch Centre of Excellence in spatial biology – Griffith News

Griffith University will establish a Centre of Excellence (CoE) in spatial biology in collaboration with Nanostring Technologies, a publicly held provider of life science tools for translational research and molecular diagnostic products.

Dr Nicholas West, from the Mucosal Immunology Research Group at Griffith Universitys Menzies Health Institute Queensland, said the CoE was the first of its type in Australia and would provide the scientific community in the Asia Pacific region with the latest in innovative immune profiling techniques.

The Griffith University Centre of Excellence in Spatial Biology will transform our capability to undertake innovative and state-of-the-art immunophenotyping across a number of diseases, he said.

The Griffith University Centre of Excellence in Spatial Biology will transform our capability to undertake innovative and state-of-the-art immunophenotyping across a number of diseases

With a focus on mucosal and tissue immunology, we will be able to provide innovative research in oncology, atopic and chronic inflammatory diseases and in data science and bioinformatics.

For instance, this offers the potential for great advances in treatment of people with cancer, where tailoring treatment requires an understanding of the tumour biology, that is, the cells driving cancer growth.

Nanostring recently launched the GeoMx Digital Spatial Profiler (DSP). Dr West said spatial biology was the next frontier.

Spatial biology allows for the comprehensive assessment and characterisation of immune cells and molecules within their morphological context.

Our ability to understand which patients will respond to different treatments has been limited by our ability to characterise the cells and molecules within the tissue environment.

GeoMx Spatial Profiling allows us to assess the cells and molecules in the tumour for a targeted understanding of the biology of the disease.

Recently this has led to new trials to determine whether key immune cells are predictive of response to immunotherapy in patients with melanoma.

This cutting-edge technology allows measuring and mapping of the spatial distribution of proteins and RNA in a tissue sample, where existing methods, which rely on the extraction of RNA or isolation of cells, have resulted in the loss of spatial information in diseased tissue.

It allows us to gain insight into the causes of disease, progression, treatment and resolution.

Deputy Vice Chancellor Research, Professor Mario Pinto said Griffith researchers were highly regarded as being at the forefront of discovery.

As a research-intensive institution, Griffith is investigating and opening doors to discovery and innovations which can help improve peoples lives.

Having access to cutting edge technology ensures a front row seat to the future.

Having access to cutting edge technology ensures a front row seat to the future

Since 2018, the University, through its leading health and medical research institute, the Menzies Health Institute Queensland, has partnered with NanoString to provide researchers and clinicians, along with their commercial partners, the capability and expertise to undertake state-of-the-art genomics, immunology and data science.

The CoE is shaping up to be the core facility of choice for this technology in the wider Asian region so there is a lot of interest in our emerging capabilities.

Given Australia and our local environment is now almost COVID free, we are able to undertake all types of basic and clinical research.

Dr West said the GeoMx Digital Spatial Profiler (DSP) enabled high throughput multiplex spatial profiling of both RNA and protein targets in a variety of sample types, including FFPE tissue sections for researcher both in translational science and clinical settings.

Since 2019, there have been more than 28 peer-reviewed research articles using GeoMx DSP published in high impact journals including Nature, Cell and Nature Medicine.

Access to this technology is considered essential for researchers in the field of immune-oncology, neuroscience and developmental biology where spatial information is key to the next breakthrough.

This partnership means we will be able to bring the latest NanoString research and development opportunities to research in the Australian community, offering efficient, comprehensive and tailored services to generate high impact research data, Dr West said.

The Centre of Excellence at Griffith University will serve as a portal for researchers across Asia Pacific to undertake research and development activities.

It will also offer a stage for researchers in the spatial biology community to develop multi-centre collaborations to drive the next transformation in translational science.

For further information on access to the GeoMx Spatial Profiling technology visit http://www.griffith.edu.au/griffith-health/systems-biology-data-science or email Dr West at [emailprotected]

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Griffith and Nanostring launch Centre of Excellence in spatial biology - Griffith News

Immunology

A Toronto doctor says covered patios aren’t much safer than being inside – blogTO

As thepandemic continues, many restaurants have turned to covered and heated outdoor patios to maintain business. However, an expert is now saying that this isn't much safer than being indoors.

University of Toronto doctor and professor in the immunology departmentEleanor Fish told HuffPost Canadathat patios with makeshift tents defeatthe purpose of actuallybeing outside.

"Outdoors is meant to be outdoors," Fish said, adding that patios worked in the summer when people could social distance and air could flow freely.

"As soon as you start enclosing space, you can fool yourself that it's still outdoors, but the reality is that unless you have air circulating to the outside very efficiently, people are putting themselves at risk."

As we know, good ventilation and airflow can help reduce the spread of COVID-19as airborne transmission is possible.

However, Fish went on to say that "as soon as you start putting walls up, you're creating an indoor space" and "you're circulating [the virus] indoors without venting it."

Many restaurants and bars across the country and across Toronto have revamped their patios with heat lamps and tented or transparent walls.

In fact, Toronto's biggest heated and covered patio yet, called The Marquee at Cabana's waterfront, opened last month. Antler, a restaurant known for its game meats, also opened a tented and heated patio called Antler Hunt Camp just over a week ago.

While Fishsaidshe understands that people miss their friends and want a social connection, she added that this is not the way to move forward.

"I think it's really risky behaviour for people to be out and about."

Instead, she suggests supporting the restaurant industry by ordering food for delivery or arranging curbside pickup.

"We shouldn't be going to any sort of outdoor patio at this stage of the game."

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A Toronto doctor says covered patios aren't much safer than being inside - blogTO

Immunology

Study sheds new light on the immune system response to COVID-19 – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Nov 16 2020

A team of immunology experts from research organizations in Belgium and the UK has come together to apply their pioneering research methods to put individuals' COVID-19 responses under the microscope.

Published today in the journal Clinical and Translational Immunology, their research adds to the developing picture of the immune system response and our understanding of the immunological features associated with the development of severe and life-threatening disease following COVID-19.

This understanding is crucial to guide the development of effective healthcare and 'early-warning' systems to identify and treat those at risk of a severe response.

One of the most puzzling questions about the global COVID-19 pandemic is why individuals show such a diverse response. Some people don't show any symptoms, termed 'silent spreaders', whereas some COVID-19 patients require intensive care support as their immune response becomes extreme.

Age and underlying health conditions are known to increase the risk of a severe response but the underlying reasons for the hyperactive immune response seen in some individuals are unexplained, although likely to be due to many factors contributing together.

To investigate the immune system variations that might explain the spectrum of responses, teams of researchers from the VIB Centre for Brain and Disease Research and KU Leuven in Belgium and the Babraham Institute in the UK worked with members of the CONTAGIOUS consortium to compare the immune system response to COVID-19 in patients showing mild-moderate or severe effects, using healthy individuals as a control group.

One of our main motivations for undertaking this research was to understand the complexities of the immune system response occurring in COVID-19 and identify what the hallmarks of severe illness are. We believe that the open sharing of data is key to beating this challenge and so established this data set to allow others to probe and analyze the data independently."

Adrian Liston, Professor and Senior Group Leader, Babraham Institute

The researchers specifically looked at the presence of T cells - immune cells with a diverse set of functions depending on their sub-type, with 'cytotoxic' T cells able to kill virus-infected cells directly, while other 'helper' T cell types modulate the action of other immune cells.

The researchers used flow cytometry to separate out the cells of interest from the participants' blood, based on T cell identification markers, cell activation markers, and cytokine cell signaling molecules.

Surprisingly, the T cell response in the blood of COVID-19 patients classified as severe showed few differences when compared to healthy volunteers. This is in contrast to what would usually be seen after a viral infection, such as the 'flu.

However, the researchers identified an increase in T cells producing a suppressor of cell inflammation called interleukin 10 (IL-10). IL-10 production is a hallmark of activated regulatory T cells present in tissues such as the lungs. While rare in healthy individuals, the researchers were able to detect a large increase in the number of these cells in severe COVID-19 patients.

Potentially, monitoring the level of IL-10 could provide a warning light of disease progression, but the researchers state that larger-scale studies are required to confirm these findings.

"We've made progress in identifying the differences between a helpful and harmful immune response in COVID-19 patients. The way forward requires an expanded study, looking at much larger numbers of patients, and also a longitudinal study, following up patients after an illness. This work is already underway, and the data will be available within months," says Professor Stephanie Humblet-Baron, at the KU Leuven in Belgium.

"This is part of an unprecedented push to understand the immunology of COVID-19", concludes Professor Liston. "Our understanding of the immunology of this infection has progressed faster than for any other virus in human history - and it is making a real difference in treatment. Clinical strategies, such as switching to dexamethasone, have arisen from a better understanding of the immune pathology of the virus, and survival rates are increasing because of it".

Source:

Journal reference:

Neumann, J., et al. (2020) Increased IL10producing regulatory T cells are characteristic of severe cases of COVID19. Clinical & Translational Immunology. doi.org/10.1002/cti2.1204

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Study sheds new light on the immune system response to COVID-19 - News-Medical.Net

Immunology

FDA-Approved Peanut Immunotherapy Protocol Comes With a Cost – Medscape

Peanut allergy immunotherapy now comes with approval from the US Food and Drug Administration (FDA), but it also comes with protocols, standards, and paperwork. Whether it will be widely adopted has yet to be determined.

A few dozen allergists around the world have been offering food allergy immunotherapy for many years, having developed their own measuring techniques using store-bought food.

But the vast majority of allergists are not interested in developing home-grown treatments, not only because it involves research and development, but also because it comes with legal risks.

"Finally we have another treatment option," said Edwin Kim, MD, from the UNC Allergy and Immunology Clinic in Chapel Hill, North Carolina. "This is what we were waiting for. It's not cowboy stuff; this works."

In January, the FDA approved peanut allergen powder (Palforzia) for patients 4 to 17 years of age, as reported by Medscape Medical News.

The pill contains measured doses of peanut flour and comes with a protocol that will allow allergists to bring patients to a peanut tolerance of 300mg (about onepeanut) and a black-box warning about anaphylaxis risk.

And before allergists can prescribe it, they must take a Risk Evaluation and Mitigation Strategy course to learn about dosing and the allergic reaction protocol.

"That may scare some away," said Kim, who discussed the FDA-approved option during his presentation at the American College of Allergy, Asthma& Immunology 2020 Annual Scientific Meeting.

Allergic reaction, including the potential for anaphylaxis, has always been an issue with immunotherapy.

"People make the argument that there is a difference" between an expected allergic reaction such as one that occurs after the administration of immunotherapy and an unexpected reaction, he said. Because an expected reaction can be treated quickly, "some feel these expected reactions don't matter so much."

"Others say a reaction is a reaction," and argue that if a treatment causes reaction, then it doesn't make sense, he explained.

It comes down to patients they must be willing to take a risk to develop tolerance and improve their quality of life and the allergists willing to treat them.

The peanut powder involves paperwork, preauthorization forms, denials of care, a higher price tag, regimented procedures, and a prerequisite number of visits with patients. "Not everyone will want to do this," said Kim.

This product offers some reassurance, and that matters.

The regimen involves three phases. During initial dose escalation, five doses are administered in the office on day1. Then, over the next 6 months, updoses are administered during 11 in-office sessions and a 300mg tolerance is achieved. Finally, to maintain tolerance to one peanut, daily doses are administered at home.

The drug cost alone is about $4200 a year, according to Institute for Clinical and Economic Review. Peanut flour from the grocery store is cheaper, but comes with the risk of bacteria or other contamination.

"This product offers some reassurance, and that matters," Kim said.

It's good to have more options for food allergy treatment. "We need a more proactive way to treat food allergy; avoidance is not good enough," he explained. "And presumably, at some point, the patient will be able to eat a grocery-store peanut instead of buying the pills."

But not all allergists will be able to make the protocol work. And it's not clear whether there is room to alter treatment and offer patients with a higher tolerance a higher starting dose. What we do know, though, is that "the product leaves little room for 'the art of medicine'," Kim said.

That art is practiced by Arnon Elizur, MD, from the Shamir Medical Center in Tzrifin, Israel, but it's backed by a rigid home-grown protocol.

Since 2010, he has treated 1800 patients for peanut allergy, updosing slowly to a tolerance of 3000mg of peanut, the equivalent of 10 peanuts. He keeps the maintenance dose at four peanuts (1200mg). His center takes a personalized approach, starting patients on the highest dose they can tolerate and working up, with daily patient check-ins from home and a staff available around the clock to answer questions and deal with reactions.

"We aim for full sensitization," Elizur told Medscape Medical News.

The peanut pill is "a big step forward" for immunotherapy, he said. It is "a standardized product, checked for bacteria and allergen content, which is available to a wide community of physicians."

But, he pointed out, "it's expensive." And it's only for peanut. "There are millions of food-allergic patients around the world dying from adverse reactions to many different kinds of food. We don't want to wait for years for a product for all of them. We can use the actual food."

He questions the lifelong maintenance protocol with a daily 300mg pill. "If you can't eat a peanut, why would you buy a drug that's a peanut?" he asked.

He also said he's disappointed that the product is not indicated for adults.

At the Shamir clinic, reactions are closely monitored. "Some are mild, others we treat with autoinjectors, epinephrine," he reported. "Those are the most undesirable."

Data from his center show that reactions occur in about 15% of patients. But his treatment success rates are good. In an average of 8 months, he is able to get 80% of his adult patients to full sensitization.

But it's not for all patients or for all clinics, he acknowledged. "We continue to look at this balance in quality of life throughout the process. Our goal is to improve the quality-of-life threshold."

Treatment that involves "native food" is "a lot of work" and requires "a lot of investment," Elizur said. His center uses a web reporting system to maintain a 24/7 dialog with patients, "and we look at the reports every day." They also have a physician on call at all times. "Not everyone can commit to providing care throughout the day and night."

His center charges the equivalent of $US3000 per food allergy treated. "That's whether it takes 6 months or 2 years," he said.

There are more than 1000 people on his 3-year waiting list.

Immunotherapy is not easy to do, whether it's FDA-approved or not.

"This is the first year that the American College of Allergy, Asthma, and Immunology is not hosting a procon debate on oral immunotherapy," Kim pointed out. "We have a therapy now."

However, the pandemic has slowed treatment uptake. "Immunotherapy is not easy to do, whether it's FDA-approved or not," he explained. With at least 11 doctor visits in the first 6 months each visit is between 30 minutes and 2 to 3 hours it hasn't been possible to set up this year. "It's not ideal."

It will be interesting to see "how this will roll out and how it will be adopted," Kim said. "From a food allergy point of view, the next 12 months are going to be very interesting."

Kim reports receiving consulting honorarium from Aimmune, the maker of Palforzia; being on the clinical medical advisory board for DBV Technologies; and consulting for DBV, Aimmune, Allakos, Allergenis, Ukko Incorporated, Vibrant America, Duke Clinical Research Institute, and Kenota Health. Elizur has The disclosed no relevant financial relationships.

American College of Allergy, Asthma & Immunology (ACAAI) 2020 Annual Scientific Meeting.

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FDA-Approved Peanut Immunotherapy Protocol Comes With a Cost - Medscape

Immunology

RAPT Therapeutics Reports Third Quarter 2020 Financial Results – BioSpace

SOUTH SAN FRANCISCO, Calif., Nov. 16, 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 reported financial results for the third quarter ended September 30, 2020 and provided an update on recent operational and business progress.

Earlier today, we reported positive initial data from our ongoing Phase 1/2 clinical trial evaluating FLX475 in multiple cancer indications, said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. With the advancement of this program and continued enrollment for our ongoing Phase 1b study of RPT193 in atopic dermatitis, which we now expect to read out in the first half of 2021, we are well positioned for multiple catalysts in 2021.

Financial Results for the Third Quarter and Nine Months Ended September 30, 2020

Third Quarter Ended September 30, 2020Net loss for the third quarter of 2020 was $14.6 million, compared to $10.0 million for the third quarter of 2019.

Research and development expenses for the third quarter of 2020 were $12.9 million, compared to $8.6 million for the same period in 2019 due to increased clinical costs for FLX475 and RPT193, increased personnel costs and stock-based compensation expense, an increase in preclinical program costs and laboratory supplies.

General and administrative expenses for the third quarter of 2020 were $3.2million, compared to $1.7million for the same period of 2019. The increase was primarily due to an increase in stock-based compensation expense, personnel costs, legal and accounting fees and insurance expense offset by a decrease in consulting costs.

Nine Months Ended September 30, 2020Net loss for the nine months ended September 30, 2020 was $40.2 million, compared to $29.8 million for the same period in 2019.

Research and development expenses for the nine months ended September 30, 2020 were $34.6 million, compared to $24.7 million for the same period in 2019. The increase was primarily due to an increase in clinical costs relating to FLX475 and RPT193, increased preclinical program costs as well as increased stock-based compensation and personnel expenses, offset by decreases in lab supplies and travel costs.

General and administrative expenses for the nine months ended September 30, 2020 were $9.3million, compared to $6.1million for the same period of 2019. The increase in general and administrative expenses was primarily due to increased stock-based compensation expense, increased personnel costs, an increase in legal and accounting fees as well as insurance expense offset by a decrease in travel and consulting costs.

As of September 30, 2020, we had cash and cash equivalents and marketable securities of $122.8 million.

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 clinical development progress and the timing of results from clinical trials of FLX475 and RPT193. 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 most recent Form 10-Q filed with the Securities and Exchange Commission 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

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RAPT Therapeutics Reports Third Quarter 2020 Financial Results - BioSpace

Immunology

RAPT Therapeutics Reports Positive Initial Data from Ongoing Phase 1/2 Clinical Trial of FLX475 in Multiple Cancer Indications – BioSpace

-Evidence of Monotherapy and Combination Activity in Charged Tumor Types--Company Advances Several Cohorts into Phase 2 Expansions--Conference Call and Webcast to be Held at 8:30 a.m. ET Today-

SOUTH SAN FRANCISCO, Calif., Nov. 16, 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 positive initial clinical data from its ongoing Phase 1/2 trial for FLX475 in multiple cancer indications.

Initial observations as of November 10, 2020 from the ongoing trial for FLX475 include preliminary:

In addition, FLX475 demonstrated a favorable safety profile, both as monotherapy and in combination with pembrolizumab.

We are pleased with the early evidence of clinical activity of FLX475, both as monotherapy and in combination with pembrolizumab in multiple charged tumor types, said Brian Wong, M.D., Ph.D., President and CEO of RAPT. Based on these encouraging data, we have determined that three cancer indications, EBV+ lymphoma, nasopharyngeal cancer and head and neck cancer, have generated sufficient early evidence of efficacy to advance into expanded Phase 2 evaluation. We continue to enroll patients and generate data in this multi-cohort, multi-indication trial and look forward to providing updates on all remaining cohorts and additional go-forward decisions next year.

Scott Antonia, M.D., PhD., Professor of Medicine and Director of the Duke Cancer Institute Center for Cancer Immunotherapy and a member of RAPTs Scientific Advisory Board, added, FLX475 is a potent non-depleting CCR4 antagonist that is designed to block regulatory T cells that interfere with an effective anti-tumor immune response. These data are particularly impressive as the immunotherapy field has long recognized Treg as important targets in oncology, but until FLX475, others have not been able to selectively target these cells in the tumor microenvironment without affecting beneficial cells. These data demonstrate that RAPTs oral small molecule approach with FLX475 holds promise in treating a variety of charged cancers.

Charged cancers are tumors that contain high levels of both regulatory T cells (Treg) and CD8 T cells and express high levels of the ligands for CCR4.

Phase 1/2 Clinical Trial DesignThe ongoing open-label Phase 1/2 study is enrolling patients with multiple types of cancer at leading cancer centers across the United States, Australia and Asia. The Phase 1 portion of the trial is focused on evaluating the safety, pharmacokinetics and pharmacodynamics of FLX475 as a monotherapy and in combination with pembrolizumab. The Phase 2 portion is designed to evaluate the degree of antitumor activity of FLX475 as a monotherapy and in combination with pembrolizumab specifically in patients with several types of charged tumors. Changes in the tumor microenvironment and other biomarkers are being evaluated in both phases of the study. For more information please visit clinicaltrials.gov identifierNCT03674567.

Phase 1 Dose Escalation DataThe dose escalation Phase 1 portion of the trial enrolled a total of 37 patients with cancers of different types. Nineteen patients were treated with one of four doses (25 mg, 50 mg, 75 mg or 100 mg once daily) of FLX475 monotherapy and 18 were treated with one of three doses (50 mg, 75 mg or 100 mg once daily) of FLX475 in combination with the standard dose of pembrolizumab. Disease control, defined as a best response of stable disease (SD), an unconfirmed or confirmed partial response (PR) or complete response (CR), was observed in 14 of the 17 evaluable monotherapy patients, including an unconfirmed partial response in a patient with relapsed metastatic cervical cancer. In the combination cohorts, disease control was observed in 13 of the 14 evaluable patients. This includes two confirmed partial responses: a patient with NSCLC who had progressed on prior checkpoint treatment (atezolizumab) and who remains on study after 18 months of treatment, and a patient with checkpoint inhibitor-nave urothelial cancer who was on study for over nine months of treatment. In addition, preliminary data show an increase in the CD8 to Treg ratio after treatment, which is consistent with the hypothesis that a CCR4 antagonist can block the recruitment of tumor Treg, increase the CD8 to Treg ratio and potentially enhance antitumor immunity.

The Phase 1 results also show FLX475 had a favorable safety profile, with no maximum tolerated dose reached. Two dose-limiting toxicities (DLTs) of asymptomatic QTc prolongation were observed in the monotherapy cohorts, one in the 75 mg cohort and one in the 100 mg cohort. No DLTs were observed in the Phase 1 combination cohorts. Based on the Phase 1 data, 100 mg was selected as the recommended Phase 2 dose for both the monotherapy and combination therapy cohorts.

Phase 2 DataThe ongoing Phase2 portion of the trial is enrolling a minimum of 80 patients with several types of charged tumors, 10 in each of eight cohorts, with four cohorts evaluating FLX475 as a monotherapy and four cohorts evaluating FLX475 in combination with pembrolizumab. The charged cancers include Epstein-Barr Virus (EBV)- or Human Papillomavirus (HPV)-associated cancers such as nasopharyngeal cancer, cervical cancer, and subsets of Hodgkin and non-Hodgkin lymphomas as well as head and neck cancer. Other charged tumor types include non-small cell lung cancer and triple-negative breast cancer. The protocol calls for expansion of cohorts to generate additional data based on promising clinical activity.

Based on the promising early results from the Phase 1/2 trial with FLX475 observed to date, RAPT has selected three cancer indications for expansion:

In these Phase 2 cohorts, FLX475 demonstrated a favorable safety profile with once-daily oral dosing both as monotherapy and in combination with pembrolizumab.

a Interim data as of November 10, 2020 from the ongoing FLX475-02 Phase 1/2 study; data subject to change.bORR = objective response rate defined as unconfirmed and confirmed PR or CRcDCR = disease control rate defined as unconfirmed and confirmed PR or CR and SD as best response

Conference Call InformationThe Company will host a webcast conference call accompanied by a slide presentation to discuss initial data from the Phase 1/2 study of FLX475 today at 8:30 a.m. Eastern Time. The call can be accessed by dialing (833) 672-0665 (domestic) or (929) 517-0344 (international) and refer to conference ID 6772479. The webcast will be available for replay for two weeks.

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, generally correlate with poor clinical outcomes 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 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines 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 clinical development progress, the significance of early results from Phase 1/2 clinical trials of FLX475 and plans with respect to Phase 2 expansions. 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 most recent Form 10-Q filed with the Securities and Exchange Commission 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

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RAPT Therapeutics Reports Positive Initial Data from Ongoing Phase 1/2 Clinical Trial of FLX475 in Multiple Cancer Indications - BioSpace

Immunology

Study reveals key role of IL-33 signaling molecule in parasite infections, other health conditions – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Nov 15 2020

De'Broski Herbert has a philosophy that's guided his career researching helminths, or parasitic worms, and their interaction with their hosts' immune systems: "Follow the worm."

The mantra of my lab since its inception has been that parasitic worms manipulate their hosts in very interesting ways to maintain their survival. SARS-CoV-2 doesn't care about staying in your body very long because it is transmitted so easily. Worms aren't spread so easily, so they have to figure out how to persist."

De'Broski Herbert, Asociate Professor of Pathobiology, School of Veterinary Medicine, University of Pennsylvania

That focus has revealed a key insight about an immune signaling molecule, the cytokine IL-33, that is important not only in parasite infections, but in a range of other health conditions, such as asthma, obesity, and eczema.

In a new study published in Science Immunology, Herbert and colleagues made insights that explain how IL-33 can both help defend the body against parasite infection, but also suppress chronic inflammation in diseases where the immune system is activated inappropriately and causes harmful pathology. A key discovery was that the activity of IL-33 depends upon which cell type is releasing it.

"Lots of people have been interested in IL-33 ever since two big genomic association studies implicated it and its receptor in the pathogenesis of asthma," Herbert says. "Other researchers have looked at it in the context of infections and others in the context of the brain and development. And everyone knew this protein was in the nucleus, but no one understood how it got out of the cell to accomplish all of these things.

"I'm excited for this work because not only do we find this cytokine in a cell type that nobody was expecting, but we also present a mechanism that no one was expecting for how it could come out."

IL-33 has been of major interest to immunologists focused on what are known as type 2 immune responses, typically associated with parasite infections or asthma and allergies.

On the parasite front, researchers knew that IL-33 acted in part to "wake up" the immune system to the presence of a worm infection. In a mouse model, animals lacking IL-33 sustain worm infections much longer than those with IL-33 intact.

To find out whether it mattered which cell type was releasing the IL-33 signaling molecule, Herbert and colleagues used special mouse model in which only myeloid antigen-presenting cells (immune cells), or epithelial cells (those that line mucosal surfaces), failed to release IL-33.

"Sure enough, we found that when animals lacking the myeloid-derived IL-33 experienced a hookworm infection, they eliminated those hookworms quite fast," Herbert says.

Mice lacking IL-33 in the epithelial cells, however, were not able to readily clear the infection. The same results held up in another rodent model, this one of roundworm infection.

Dendritic cells, a type of myeloid antigen-presenting cell, produce IL-33, and further experiments showed that the cytokine produced by these cells supported a specific population of regulatory T cells (Tregs), which are cells "whose whole purpose is to suppress the immune response," Herbert says.

Now understanding that dendritic cells were key to supporting Tregs, the researchers wanted to understand how the dendritic cells were delivering the IL-33. The team screened dendritic cells from mice with and without IL-33, identifying a protein called perforin-2 to be suppressed in expression from myeloid cells lacking IL-33.

Perforin-2, as its name suggests, forms a pore that spans the cell membrane, like a tunnel in a hillside, allowing the transport of proteins in and out.

The find made complete sense to the researchers, providing an explanation for how dendritic cells could promote the release of IL-33 into the tissues to interact with Tregs. And when Herbert and colleagues experimentally eliminated perforin-2 from dendritic cells, they saw a subsequent lack of Treg growth.

To connect the findings in their animal model and lab dishes to humans, the team utilized patient samples from Penn otolaryngologist Noam Cohen.

They found perforin-2 at the plasma membrane of cells from polyps removed from patients with chronic rhinosinusitis, suggesting that the significance of the findings extends to human health.

The study paves the way for even more translational work in immunology--and worms are to thank. "It's kind of the missing link," Herbert says. "It opens up a whole new direction for understanding how this cytokine could be involved in obesty, inflammatory bowel disease, Crohn's, asthma, and development."

Source:

Journal reference:

Hung, L-Y., et al. (2020) Cellular context of IL-33 expression dictates impact on anti-helminth immunity. Science Immunology. doi.org/10.1126/sciimmunol.abc6259.

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Study reveals key role of IL-33 signaling molecule in parasite infections, other health conditions - News-Medical.Net

Immunology

RAPT Therapeutics to Announce Initial Data from Phase 1/2 Clinical Trial of FLX475 in Multiple Cancer Indications – BioSpace

SOUTH SAN FRANCISCO, Calif., Nov. 15, 2020 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), 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, today announced that the Company plans to present initial data from its Phase 1/2 clinical trial of FLX475 in patients with multiple cancer indications in a premarket press release and webcast on Monday, November 16, 2020.

RAPT will host a conference call accompanied by a slide presentation at 8:30 a.m. ET on Monday, November 16th. The live webcast and audio archive of the presentation may be accessed on the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations. The call can be accessed by dialing (833) 672-0665 (domestic) or (929) 517-0344 (international) and refer to conference ID 6772479. The webcast will be available for replay for two weeks. Please connect to the website 10 minutes prior to the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast.

About RAPT 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.

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

RAPT Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

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RAPT Therapeutics to Announce Initial Data from Phase 1/2 Clinical Trial of FLX475 in Multiple Cancer Indications - BioSpace

Immunology

Leading Human Immunology and Infectious Disease Experts to Join UM School of Medicines Institute of Human Virology – Newswise

Newswise Baltimore, MD, November 12, 2020 Robert C. Gallo, MD, the Homer & Martha Gudelsky Distinguished Professor in Medicine at the University of Maryland School of Medicine (UMSOM) and Co-Founder & Director of the UMSOMs Institute of Human Virology (IHV), announced today that a team of leading scientists in human immunology, virology and stem cell biology, led by Lishan Su, PhD joined IHV on October 1 with academic appointments in the UMSOM Department of Pharmacology. As part of the Maryland E-Nnovation Initiative Fund (MEIF) to recruit top research faculty and a donation to IHV from the Charles Gordon Estate, Dr. Su has been named the Charles Gordon Smith Endowed Professor for HIV Research. Dr. Su will also head IHVs Division of Virology, Pathogenesis and Cancer.

The team will include a 12-person Laboratory of Viral Pathogenesis and Immunotherapy with two faculty appointments as well as major public and private sector research funding.

Dr. Gallo made the announcement in conjunction with University of Maryland School of Medicine Dean E. Albert Reece, MD, PhD, MBA and Margaret M. McCarthy PhD, James & Carolyn Frenkil Deans Professor, Chair of the Department of Pharmacology.

Dr. Su is one of the most successful active basic researchers in America, said Dr. Gallo, who is also Co-Founder and Chairman of the International Scientific Leadership Board of the Global Virus Network. His research is groundbreaking, and we are so pleased to have him join IHV and lead our Division of Infectious Agents and Cancer, which under his sound leadership, will flourish.

Dr. McCarthy added:Dr. Sus continuing ground-breaking work in HIV and Hepatitis B will be a huge asset to the Department of Pharmacology. I look forward to working with him on advances that could open the door to new therapeutics.

Dr. Su was a faculty member in the Lineberger Comprehensive Cancer Center and Professor in the Department of Microbiology & Immunology at University of North Carolina-Chapel Hill since 1996. He received his BS degree in Microbiology from Shandong University, his PhD degree in Virology from Harvard University, and did his post-doctoral training in Stem Cell Biology & Immunology at Stanford University. He worked as a senior research scientist at SyStemix/Sandoz (Novartis), focusing on HIV-1 pathogenesis and stem cell-based gene therapy in humanized mice and in patients.

I am excited to continue and expand my research programs at the Institute of Human Virology (IHV), said Dr. Su. I have long been impressed by the Baltimore-DC area's research centers with great basic and clinical research programs. IHV, co-founded and directed by Dr. Robert Gallo, is one of the first research institutes in the U.S. to integrate basic science, population studies and clinical trials to understanding and treating human virus-induced diseases. The Department of Pharmacology, headed by Dr. Margaret McCarthy, in the University of Maryland School of Medicine, has been outstanding in developing novel therapeutics including breast cancer drugs. I look forward to working with my new colleagues at IHV and the Department of Pharmacology, and across the University of Maryland School of Medicine, to expand and translate my research programs to treating human inflammatory diseases including virus infection and cancer.

Dr. Su has extensive research experience in human immunology, virology and stem cell biology. Dr. Su made important contributions to several areas of human immunology and infectious diseases, particularly in studying human immuno-pathology of chronic virus infections. His lab at UNC-Chapel Hill published important findings in identifying novel virological and immunological mechanisms of HIV-1 pathogenesis. Furthermore, his lab established humanized mouse models with both human immune and human liver cells that support HCV or HBV infection, human immune responses and human liver fibrosis. In recent years, Dr. Sus group discovered, and focused on, the pDC-interferon axis in the immuno-pathogenesis and therapy of chronic HIV & HBV infections. The group also started investigation of the pDC-IFN axis in tumor microenvironments and in cancer immune therapy.

Im so pleased to welcome Dr. Su to our faculty. His work advances the mission of the School of Medicine, which is to provide important new knowledge in the area of immunology and chronic disease to discover new approaches for treatments, said Dean Reece, who is also University Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor. Dr. Sus stellar research capabilities will provide vital opportunities for collaboration across our Institutes and Departments.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders - most notably, HIV the virus that causes AIDS. For more information,www.ihv.organd follow us on Twitter @IHVmaryland.

About the University of Maryland School of Medicine

The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States and continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Marylands Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global vision, with research and treatment facilities in more than 30 countries around the world. For more information, visitwww.medschool.umaryland.edu.

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Leading Human Immunology and Infectious Disease Experts to Join UM School of Medicines Institute of Human Virology - Newswise

Immunology

Study Finds Kids Develop Different Antibodies When They Get COVID-19 – Healthline

One of the striking things about COVID-19 is that children who have contracted the new coronavirus rarely develop the kinds of severe respiratory and other symptoms seen in adults.

In addition, most children who develop COVID-19 have mild or no symptoms.

This doesnt mean children are immune to the new coronavirus.

A small number of children with COVID-19 can develop a serious condition called multisystem inflammatory syndrome in children (MIS-C). Scientists arent certain, though, why some children get very sick and others dont.

A new study published Nov. 5 in the journal Nature Immunology adds to our understanding of the differences between how children and adults respond to SARS-CoV-2.

Researchers from Columbia University and other institutions found that childrens immune response to SARS-CoV-2 is distinct from that of adults. This was true even in children who developed MISC-C.

Shane Crotty, PhD, a virologist at the La Jolla Institute for Immunology, said this finding wasnt a given.

Children definitely have a different disease outcome from adults, he said, but that could be for a lot of different reasons.

After analyzing blood samples taken from adults and children, researchers saw that children who had contracted the new coronavirus produced lower levels of neutralizing antibodies and fewer types of antibodies.

The immune system can produce many different antibodies specific to a virus. Neutralizing antibodies bind in a way that blocks infection.

The results of the study dont mean that childrens immune response was weaker, because that implies that more is better, said Dr. Ravi Jhaveri, associate division head of infectious disease and professor of pediatrics (infectious diseases) at the Ann & Robert H. Lurie Childrens Hospital of Chicago.

The adult patients with the worst symptoms of ARDS [acute respiratory distress syndrome] had the highest levels of antibody, Jhaveri said, while children with varying levels of symptoms, mostly milder, had lower responses.

Even among adults, those with severe symptoms had higher levels of neutralizing antibodies compared to adults with mild symptoms.

Again, the higher levels of neutralizing antibodies didnt correlate with better disease outcomes.

People tend to oversimplify that neutralization is all we should care about, but this may not be the whole story, Jhaveri said. Sometimes the best antibodies are the ones that help the immune cells find and destroy a virus.

Researchers didnt look at this kind of immune activity.

Sean Diehl, PhD, an associate professor of microbiology and molecular genetics at the University of Vermont, said another interesting finding of the study is that the adults produced antibodies that bound to more parts of the virus.

Adults are targeting both the outer spike protein, as well as the nucleocapsid that binds to and protects the genome of the virus, he said. But kids are only making antibodies against the spike protein.

This could have implications for coronavirus testing. Some antibody tests, including those made by Abbott and Roche, look only for antibodies that bind to the nucleocapsid. These tests may miss children who currently have the new coronavirus or who had an infection in the past.

Diehl said adults may be producing more types of antibodies because they have a higher viral load than children. The researchers didnt measure how much virus people had in their body, so this connection isnt clear.

However, the fact that both children and adults produced neutralizing antibodies against the spike protein bodes well for COVID-19 vaccines, Diehl said.

Many vaccine candidates currently being studied target the spike protein. Preliminary data from some phase 3 trials suggest that these vaccines are effective in adults. This suggests they may also work in children, who havent been included in many of the ongoing trials.

In the new study, researchers analyzed antibodies from a single point in time from 79 participants in four groups:

The study was too small to show whether childrens antibody levels differed with age. The blood samples also came from one hospital in one region of the country, so the results may not apply to everyone.

Alessandro Sette, Dr. Biol.Sci., an immunologist at the La Jolla Institute for Immunology in California, said the results reinforce the idea that its not just antibodies that determine how sick someone gets from COVID-19, but many factors are involved.

We already know that people with other medical conditions, such as obesity, cardiovascular disease, and diabetes, are more at risk for severe disease.

In addition, Diehl said that in certain adults with severe COVID-19, some of the damage is caused by an overreaction of the immune system rather than the virus itself.

In these people, the immune system is acting quite strongly and causing a lot of collateral damage, Diehl said.

Its not clear, though, why some children have more severe disease than others. The researchers offered several possible reasons.

The lower levels of neutralizing antibodies in children may predispose them to persistent infection in other parts of the body, leading to MISC-C.

Or the presence of non-neutralizing antibodies could lead to a condition known as antibody-dependent enhancement (ADE), which is known to occur in other viral infections.

More research in this area is needed.

While the new study looked at antibodies proteins that bind to the virus to prevent infection the immune system also has a cellular component.

This includes killer T cells that attack cells invaded by the virus, and helper T cells that help coordinate the immune response.

Some data show that adults who have a more benign outcome have good T-cell responses both helper and killer T cells and also antibody responses, Sette said.

A persons T-cell response may be a better indicator of how sick a person gets with COVID-19, according to Sette. In the new study, the researchers didnt measure peoples cellular immune response.

Jhaveri also sees a possible role for T cells in determining the severity of illness.

It may be that a childs cellular response is really strong and the antibodies have to do less work, Jhaveri said, and the opposite is true for adults.

Some researchers have proposed that T cells from people who have recovered from COVID-19 could be used to treat other people, similar to how convalescent plasma therapy is thought to work.

Although the new study shows a difference in antibody response between children and adults, Jhaveri said the data dont indicate whether children are more likely to transmit or contract the new coronavirus.

Crotty said results from other studies on this topic have been mixed.

Ive seen data that seem to indicate that kids get infected just as much [as adults] but dont get sick, he said. And Ive seen other data that indicate that kids dont get infected as much.

More research is needed to fully understand how childrens immune systems respond to the coronavirus, but this can be challenging simply because children with COVID-19 dont get as sick.

You dont have access to as many cases in children to study, Sette said, because many may go undetected.

That is one of the things that is very important about this study, he added. It is one of the first studies to really have a very careful, quantitative analysis of the antibody response in kids with and without MISC-C syndrome.

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Study Finds Kids Develop Different Antibodies When They Get COVID-19 - Healthline