(Press-News.org) LOS ANGELES — Medical scientists at the University of Southern California (USC) have bred a first-of-its-kind mouse model that possesses an immune response system more like a human's. The discovery makes way for quicker and more cost-effective development of next-generation drugs to treat human diseases like cancer, diabetes and tuberculosis.
Medical researchers have long used mice and rats to help formulate new drugs and vaccines, in part because their genetic and biological characteristics closely parallel human physiology. But mice are not humans, and many experimental drugs that work extraordinarily well in rodents fail miserably when tested in people. One such drug, α-galactosylceramide (α-GalCer), essentially wipes out cancerous tumors in mice by activating the body's immune system; for reasons not entirely clear, the drug does not trigger the same response in people with cancer.
Scientists hypothesize that the failure to translate is due to subtle differences between the CD1d molecules in mice and humans and how they respond to tumors and infection. CD1d molecules are found on certain cells that trigger the body's innate immune response. In a study to be published by the Proceedings of the National Academy of Sciences the week of Feb. 4, USC researchers describe how they genetically engineered mice to express CD1d molecules that look more like those in humans and in more similar proportions. More importantly, the humanized CD1d molecules effectively trigger natural killer T (NKT) cells—a recently discovered type of white blood cell that attacks tumors and infection—in live animals when exposed to α-GalCer.
"It's the best model we have in the field," said Weiming Yuan, Ph.D., assistant professor of molecular microbiology and immunology at the Keck School of Medicine of USC and principal investigator of the study. "We've basically set a platform to fast-track the identification of immunotherapies that can kill cancer and also make vaccines stronger."
Once activated, NKT cells react in a matter of hours whereas other T cells may take days. This rapid response makes them difficult to study, but also an ideal target for drug-makers. Yuan's humanized mouse allows scientists to more accurately test the viability of those NKT cell-targeting drugs before going to human clinical trials.
"Before, it would have been a guess as to whether the drug would work in people. Now, the chance of success goes from 1 out of 100 to 1 out of 5," Yuan said.
Yuan and colleagues have yet to demonstrate the effects of inserting a more human-like version of the final component of the CD1d/NKT system, the T cell receptor. More experiments are necessary to determine why α-GalCer is ineffective in treating people with cancer and to develop novel α-GalCer derivatives that work with the human immune system.
###Co-authors include Xiangshu Wen, Seil Kim and Agnieszka Lawrenczyk of the Keck School of Medicine; Ping Rao of the UCLA Immunogenetics Center and Department of Pathology; Leandro J. Carreño and Steven A. Porcelli of the Albert Einstein College of Medicine at Yeshiva University; and Peter Cresswell of the Yale University School of Medicine. The research was supported by the National Institutes of Health (R01 AI091987, R01 AI059167, R01 AI045889), the Harry Lloyd Charitable Trust, the Margaret Early Medical Research Trust, and the Howard Hughes Medical Institute.
USC scientists design mouse with more human-like immune response
Discovery could help accelerate development of more effective immunotherapies
2013-02-05
ELSE PRESS RELEASES FROM THIS DATE:
Cells predict onset of graft-versus-host disease in men receiving BMTs from female donors
2013-02-05
STANFORD, Calif. — Stanford University School of Medicine investigators have identified a clutch of cells that — if seen in a male patient's blood after receiving a brand-new immune system in the form of a bone-marrow transplant from a female donor — herald the onset of chronic graft-versus-host disease, or cGVHD. In this devastating syndrome, the patient's tissues come under a vicious and enduring assault by the transplanted cells.
"The overwhelming majority of patients who have these cells in their blood either have or will develop cGVHD within one to three months," ...
3D printing breakthrough with human embryonic stem cells
2013-02-05
A team of researchers from Scotland has used a novel 3D printing technique to arrange human embryonic stem cells (hESCs) for the very first time.
It is hoped that this breakthrough, which has been published today, 5 February, in the journal Biofabrication, will allow three-dimensional tissues and structures to be created using hESCs, which could, amongst other things, speed up and improve the process of drug testing.
In the field of biofabrication, great advances have been made in recent years towards fabricating three-dimensional tissues and organs by combining artificial ...
'Default' options influence patient choices in advance care directives, Penn study shows
2013-02-05
PHILADELPHIA – Advance care directives allow patients to provide instructions about their preferences for the care they would like to receive if they develop an illness or a life-threatening injury and lose the capacity to make decisions for themselves. While many people may assume that patients have strong preferences for the type and aggressiveness of care they wish to receive near life's end, a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania suggests that for many patients, preferences for end-of-life care are constructed ...
Experimental therapy crosses blood-brain barrier to treat neurological disease
2013-02-05
CINCINNATI – Researchers have overcome a major challenge to treating brain diseases by engineering an experimental molecular therapy that crosses the blood-brain barrier to reverse neurological lysosomal storage disease in mice.
Posted online in PNAS Early Edition on Feb. 4, the study was led by scientists at Cincinnati Children's Hospital Medical Center.
"This study provides a non-invasive procedure that targets the blood-brain barrier and delivers large-molecule therapeutic agents to treat neurological lysosomal storage disorders," said Dao Pan, PhD, principal investigator ...
Body language can predict outcomes for recovering alcoholics
2013-02-05
To predict whether a problem drinker will hit the bottle again, ignore what they say and watch their body language for displays of shame, a University of British Columbia study finds.
The study, which explored drinking and health outcomes in newly sober recovering alcoholics, is the first to show that physical manifestations of shame – from slumped shoulders to narrow chests – can directly predict a relapse in people who struggle with substances.
"Our study finds that how much shame people display can strongly predict not only whether they will go on to relapse, but ...
20 hours of TV a week almost halves sperm count
2013-02-05
Healthy young men who watch TV for more than 20 hours a week have almost half the sperm count of men who watch very little TV, indicates a study published online in the British Journal of Sports Medicine.
Conversely, men who do 15 or more hours of moderate to vigorous exercise every week have sperm counts that are 73% higher than those who exercise little, the findings show.
Semen quality seems to have deteriorated over the past few decades, although it's not clear why, say the authors.
To find out if an increasingly sedentary lifestyle might be a contributory ...
The last Neanderthals of southern Iberia did not coexist with modern humans
2013-02-05
The theory that the last Neanderthals –Homo neanderthalensis– persisted in southern Iberia at the same time that modern humans –Homo sapiens– advanced in the northern part of the peninsula, has been widely accepted by the scientific community during the last twenty years. An international study, in which researchers of the Spanish National Distance Education University (UNED) participate, questions this hypothesis.
"It is improbable that the last Neanderthals of central and southern Iberia would have persisted until such a late date, approximately 30,000 years ago, as ...
Mutations in ASXL3 cause problems similar to Bohring-Opitz syndrome
2013-02-05
Mutations which affect the gene ASXL3 cause a novel syndrome similar to Bohring-Opitz syndrome, finds a study published in BioMed Central's open access journal Genome Medicine. This molecular definition distinguishes these children from those with Bohring-Opitz, and other similar syndromes, and highlights a technique able to help define rare diseases.
When Dr Ropers from the Max-Planck Institute for Molecular Genetics in Berlin found a child with non-specific symptoms, including small size at birth, difficulties with movement and feeding, severe intellectual disability, ...
Researchers pioneer treatment for viral infection common in children
2013-02-05
Researchers at Imperial College London have discovered a new way in which a very common childhood disease could be treated.
In the first year of life, 65 per cent of babies get infected by Respiratory Syncytial Virus (RSV). This causes bronchiolitis, and is thought to kill nearly 200,000 children every year worldwide.
In 1966 and 1967, vaccines were tested for RSV. These had disastrous effects on the immune response, leading to a worsening of the disease and, in many cases, death. Scientists have so far not been able to fully explain this effect, which continues to ...
Could the humble sea urchin hold the key to carbon capture?
2013-02-05
A chance discovery that sea urchins use Nickel ions to harness carbon dioxide from the sea to grow their exoskeleton could be the key to capturing tonnes of CO2 from the atmosphere.
Experts at Newcastle University, UK, have discovered that in the presence of a Nickel catalyst, CO2 can be converted rapidly and cheaply into the harmless, solid mineral, calcium or magnesium carbonate.
This discovery, which is published today in the academic journal Catalysis Science & Technology, has the potential to revolutionise the way we capture and store carbon enabling us to significantly ...
LAST 30 PRESS RELEASES:
Sinuses prevented prehistoric croc relatives from deep diving
Spirited away: Key protein aids transport within plant cells
Britain’s brass bands older than we thought and invented by soldiers from the Napoleonic Wars, new study reveals
The Lancet: Health threats of climate change reach record-breaking levels, as experts call for trillions of dollars spent on fossil fuels to be redirected towards protecting people’s health, lives and
‘Weekend warrior’ exercise pattern may equal more frequent sessions for lowering cognitive decline risk
Physical activity of any intensity linked to lower risk of death after dementia diagnosis
Brain changes seen in lifetime cannabis users may not be causal
For the love of suckers: Volunteers contribute to research on key freshwater fishes
Bill and Mary Anne Dingus commit $1M to fund Human Impacts on the Earth Fund at Rice
Most patients can continue GLP-1 anti-obesity drugs before surgery
Computational tool developed to predict immunotherapy outcomes for patients with metastatic breast cancer
Cerebral embolic protection by geographic region
12 new Oriental weevil species discovered using advanced imaging tools
Ultrasound can be used as search and rescue tool for the brain
Department of Defense funds study of gene therapy for muscular degeneration
People’s exposure to toxic chemicals declined in the U.S. following listing under California law
Trauma, homelessness afflict gender affirming care patients at higher rates
New $5 million DoE award supports KU startup’s green hydrogen energy research
A navigation system for microswimmers
Study finds early TAVR can be beneficial for patients with asymptomatic severe aortic stenosis
Implantable microparticles can deliver two cancer therapies at once
Early intervention in patients with asymptomatic severe aortic stenosis and myocardial fibrosis falls short of expected benefits
The surprising reason a classical computer beat a quantum computer at its own game
Researchers Aim To Get Leg Up on Bone Repair with 3D-Printed Femur
Transforming patient care: study finds bedside interdisciplinary rounds boost satisfaction for patients and providers
Radioprotective effects of licochalcone B: DNA protection, cytokine inhibition, and antioxidant boost
Complete response to encorafenib + binimetinib in BRAF V600E-mutant tumor
Gold bugs: Spectacular new fossil arthropod preserved in fool’s gold
Optimal standing positions and ventilation in airport smoking lounges
Ancient gene influences immunity of First Nations Peoples of Oceania
[Press-News.org] USC scientists design mouse with more human-like immune responseDiscovery could help accelerate development of more effective immunotherapies