Engineered T cells for type 1 diabetes move closer to clinic
Dr. Jane Buckner of the Benaroya Research Institute at Virginia Mason and Dr. David Rawlings at Seattle Children’s Research Institute are leading research to develop an engineered T-cell therapy for type 1 diabetes. Credit: Seattle Children’s

For much of the last decade, Dr. David Rawlings, director of Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies, has dreamed of developing a therapy for children with type 1 diabetes that doesn’t involve insulin injections but uses a person’s own immune cells to target and treat the disease.

Now, new research and a fresh infusion of funding bring this dream closer to reality, and nearer to opening a first-in-human clinical trial of an experimental therapy at Seattle Children’s in collaboration with research partner Benaroya Research Institute at Virginia Mason (BRI).

“What started as a dream is now within reach,” Rawlings said. “My hope is that our research will lead to a new treatment that turns off the destructive immune response leading to development of type 1 diabetes in children.”

The immune system’s imbalance in diabetes

The research led by Rawlings, who is also the Division Chief of Immunology at Seattle Children’s and a professor of pediatrics and immunology at the University of Washington School of Medicine, along with co-investigator Dr. Jane Buckner, president of BRI, focuses on T cells, the immune system’s disease-fighting .

In type 1 diabetes, specific types of immune cells called effector T cells mistakenly attack insulin-producing islet cells in the pancreas. The job of these islet cells is to sense when are rising in the bloodstream and to respond by releasing insulin.

The attack continues because other components of the immune system, regulatory T cells (Treg), do not function normally.

“A healthy requires regulatory T cells to balance the attack of effector T cells,” Rawlings said. “Regulatory T cells tell the effector T cells to calm down and limits damage to tissues like the pancreas.”

Once destroyed by the unchecked effector T cells, the islet cells can’t release insulin. Glucose levels in the bloodstream then rise unabated, causing the early symptoms of diabetes such as frequent urination, unquenched thirst, insatiable hunger and extreme fatigue.

Novel engineered T cells offer a way to restore balance in the pancreas

To stop this attack, Rawlings’ lab devised a way to genetically engineer a patients own T cells, so they function like normal Treg. The hope is that when transferred back into the patient, these engineered or edited regulatory-like T cells (edTreg) enter the pancreas, where they can help to suppress the overactive immune response, sustaining and protecting the function of the islet cells.

A paper published in Science Translational Medicine shows how the research team used gene editing techniques to target the FOXP3 gene in human T cells. By turning on FOXP3, they equipped the T cells with the instructions needed to specialize into Treg.

The resulting edTreg looked very similar to natural Treg. They also functioned like natural Treg when tested in both animal models and tissue cultures. Finally, researchers demonstrated how they could make the engineered cells antigen-specific. According to Rawlings, this feature, which is accomplished by attaching a T-cell receptor to the surface of the engineered cell, will be critical to targeting the cells to the pancreas in a diabetic patient.

Further research to validate these results will help pave the way for a phase 1 clinical trial of a type 1 diabetes cell therapy.

“This data offers the first proof that engineering by way of turning on FOXP3 is sufficient to make a functional Treg-like cell product,” he said. “Not only is it a landmark research finding, but it’s directly translatable to clinical use.”

New funding continues promising research

Much of the research to develop the edTreg has been funded through a combination of industry sponsored agreements and generous philanthropic support from The Leona M. and Harry B. Helmsley Charitable Trust.

Most recently, the Helmsley Charitable Trust awarded a new $4 million grant to Seattle Children’s and BRI to continue the diabetes research.

The grant builds on $3 million in prior funding from the Helmsley Charitable Trust and an ongoing research collaboration between the two research programs. In this next phase, the teams will work to fine tune the T-cell receptor used for the edTreg and enhance the manufacturing process used to generate the edTreg for .

“Our collaboration with BRI combines their broad expertise in finding and testing T-cell receptors from diabetic patients with our novel technology to engineer the T cells,” Rawlings said.

The best T-cell receptor will direct the edTreg to the pancreas and turn on their protective activity and, ideally, will also work for the greatest number of type 1 diabetes patients.

“We want to identify T-cell receptors that will create engineered Treg that will go to and protect the pancreas. This type of therapy could then be used to stop the destruction of that produce insulin in the pancreas to slow the progression and ultimately prevent type 1 diabetes,” said Buckner of BRI.

A dream within reach

Rawlings says the newly-funded studies will help them to establish the final cell product and key information required to establish a first-in-patient clinical trial.

He’s optimistic that the 3-year grant will give them the opportunity to complete the preclinical studies and study design required to submit an Investigational New Drug Application to the U.S. Food and Drug Administration for the approval to open a phase 1 clinical trial at Seattle Children’s and BRI.

“This is a novel technology that no other lab in the world is pursuing and that has potential major advantages over Treg therapies being studied elsewhere,” Rawlings said. “I think some in the field questioned whether our approach would actually work, and so it’s gratifying to not only have proof that it works, but to continue to generate data showing just how remarkably well it works.”


Immunotherapy, gene editing advances extend to Type 1 Diabetes


More information:
Y. Honaker el al., “Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function,” Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ … scitranslmed.aay6422

Citation:
Engineered T cells for type 1 diabetes move closer to clinic (2020, June 3)
retrieved 3 June 2020
from https://medicalxpress.com/news/2020-06-cells-diabetes-closer-clinic.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.



(Visited 1 times, 1 visits today)

Related posts:

Hong Kong to shut all schools after virus cases spike
Umfrage: Videosprechstunden bekommen in Corona-Krise Schwung
Lebanon’s neo-liberal wheels sped to a dream future, but the past applies the brakes
China vows to hit US with 'reciprocal measures' after Xinjiang sanctions
Why India cases are rising to multiple peaks
Ein Datenschatz für die Ganganalyse
Researchers identify key role of immune cells in brain development
Merkel press office staffer 'worked for years for Egyptian intelligence'
France investigates report of bodies 'left to rot' at Paris research centre
New study supports remdesivir as COVID-19 treatment
Neues Proteomik-Verfahren: Detaillierter Einblick in die gestresste Zelle
US sees latest record surge in virus cases amid wrangling over lockdown measures
Air Pollution Takes a Global Toll on Heart Health
Indoor airborne spread of coronavirus possible
Australia locks down second city as global cases top 12 million
Serbia drops plans for reimposed lockdown after days of violent protests
WHO launches global pandemic response probe
French César awards announce changes in response to Polanski #MeToo brouhaha
Airborne coronavirus transmission raises new questions and worries
Forecasts predict worse EU recession since WWII
reducing your risk of kidney stones
Scientists discover protective Alzheimer's gene and develop rapid drug-testing platform
UK declines participating in EU Covid-19 vaccine scheme over concerns of delays
Technology Bridges the Gap to Better Sight
CT of COVID-19 versus CT of influenza virus pneumonia
Bolivia's President Anez tests positive for Covid-19
Dogs May Be Good for Children’s Psychological Development
New study outlines best practices for delivering care via telehealth
What’s the Best Exercise for You? Twins Can Provide an Answer
A memory game could help us understand brain injury
Übernahme von Rhön-Klinikum AG durch Asklepios abgeschlossen
Corsicans harness the #IWas movement to challenge a culture of silence
Drug Giants Create Fund to Bolster Struggling Antibiotic Start-Ups
Coronavirus fears kept many essential workers at home in April, study finds
Stationär behandelte Bronchiolitis: Feste Nachsorgetermine möglicherweise gar nicht notwendig
Facing ridicule, France changes title for its ‘minister for attractiveness’
The Coronavirus Can Float in Indoor Air, W.H.O. Concedes
Covid-19 drug buyout: US's EU representative denies 'America First' policy on Remdesivir
Virtuelle Hämatologie/Onkologie-Jahrestagung: „Mehr Wissenschaft – mehr Hoffnung“
Streamlining acute malnutrition treatment brings same recovery in children at lower cost
A Missed Warning About Silent Coronavirus Infections
COVID-19-Studie: Studie errechnet doppelten Nutzen bei überlasteten Intensivstationen
Body of Seoul’s mayor found after massive search
Living close to green space benefits gut bacteria of urban, formula-fed infants
Regeneron Scientists Raced To Find Antibodies To Fight Covid-19. Then The Coronavirus Found Them.
DKG: Finanzierung der ambulanten Krebsberatung weiterhin nicht gesichert
Study sheds light on how cancer spreads in blood
Volunteer carpenters aim to settle reconstruction debate
At Least 5 States Set Single-Day Coronavirus Case Records
IQWiG empfiehlt kein Screening auf Hodenkrebs
Libya: Countries who supported Haftar 'bet on the losing horse', adviser to GNA says
one in six British people would refuse a vaccine – here's how to change their minds
Who Gets a Vaccine First? U.S. Considers Race in Coronavirus Plans
Supreme Court rules NY prosecutors can obtain Trump tax returns
Aktuelle ASCO-Studien zeigen hohen Stellenwert der Radioonkologie bei Kopf-Hals-Tumoren
Ten tips for looking after your back while you're sitting down
Live Coronavirus Updates: U.S. Daily Cases Surpass 59,000
Asthma und Allergien: Zusammenhang mit Schlafgewohnheiten von Jugendlichen
China's new strategy to tame second-wave virus outbreaks
Biogen engagiert sich in Deutschland im weltweiten Kampf gegen COVID-19
Schools or bars? Opening classrooms may mean hard choices
Künstliche Intelligenz im Kampf gegen das Coronavirus
A wave of independence sweeps across Africa
Virus cases jump in worst-hit trio of US, Brazil and India
MEG Teltow übernimmt urologische Praxis in Finsterwalde
Four-time Tour winner Chris Froome to leave Team INEOS at end of season
Scientists identify key factor regulating abnormal heart growth
PREDICT-Card: Wirksam gegen Bauchspeicheldrüsenkrebs - Biermann Medizin
Is it safe to visit the dentist during the pandemic?
'Consensus' that Notre-Dame spire should be rebuilt in original form
Benigner paroxysmaler Lagerungsschwindel – Letzte Therapieoption
Ultra-fine X-rays target brain cancer cells with precision
Wirkstoffe aus Kieler Meeresalgen als Mittel gegen Infektionen und Hautkrebs entdeckt
Almost 30 women accuse Paris street artist of rape, sexual assault
'Anti-vaxxers' gain traction against HPV vaccine on Facebook, study shows
Gentherapie bei Netzhautdegeneration: Was ist heute möglich? Wie geht es weiter?
George Floyd told officers 'I can't breathe' more than 20 times, transcript shows
Immediate outreach increases children's likelihood of completing PTSD screens, says researcher
Warning of possible virus resurgence, France rules out another 'total lockdown'
Implantate: Wie lassen sich Komplikationen nach der OP verringern?
Researchers uncover a critical early step of the visual process
Trump insists on re-opening schools as US Covid-19 death toll tops 3 million
Mexican president lauds Trump despite past threats, insults against Mexicans
5G networks have few health impacts, study finds
Grave Shortages of P.P.E. Gear Flare Again as Covid Cases Surge
Melbourne starts six-week lockdown on fears of second Covid-19 wave
Donald Trump 'narcissist', 'never been loved', writes niece in tell-all book
Spatial mapping method pinpoints potential new therapeutic targets in lupus
Study of 17 Million Identifies Crucial Risk Factors for Coronavirus Deaths
Nurses and midwives take the lead in providing HIV services in Eastern and Southern Africa
Brazil's President Bolsonaro taking - and pushing
Drug treatment could improve effectiveness of immunotherapy for cancer patients
Menthol cigarette ban in the US may lower number of smokers
Higher fruit, vegetable and whole grain intake linked to lower risk of diabetes
Experimental drug shows early promise against inherited form of ALS, trial indicates
Harvard, MIT sue Trump administration over revoking foreign student visas
Large-scale fall prevention study finds smaller than expected benefit
NfL outperforms other blood tests to predict and diagnose traumatic brain injury
Ivorian Prime Minister Amadou Gon Coulibaly dies at 61
Angeborene Herzfehler: Veränderungen der Hirnstruktur mit MRT schon im Mutterleib erkennen

Leave a comment

Your email address will not be published. Required fields are marked *