PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Gene therapy method targets tumor blood vessels

2013-12-27
(Press-News.org) Contact information: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Gene therapy method targets tumor blood vessels

Working in mice, researchers at Washington University School of Medicine in St. Louis report developing a gene delivery method long sought in the field of gene therapy: a deactivated virus carrying a gene of interest that can be injected into the bloodstream and make its way to the right cells.

In this early proof-of-concept study, the scientists have shown that they can target tumor blood vessels in mice without affecting healthy tissues.

"Most current gene therapies in humans involve taking cells out of the body, modifying them and putting them back in," said David T. Curiel, MD, PhD, distinguished professor of radiation oncology. "This limits gene therapy to conditions affecting tissues like the blood or bone marrow that can be removed, treated and returned to the patient. Today, even after 30 years of research, we can't inject a viral vector to deliver a gene and have it go to the right place."

But now, investigators at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine say they have designed a "targetable injectable vector" – a deactivated virus that homes in on the inner lining of tumor blood vessels and does not get stuck in the liver, a problem that has plagued past attempts.

The findings are reported Dec. 23 in PLOS ONE.

Building on their own previous work and others', the researchers engineered this viral vector to turn on its gene payload only in the abnormal blood vessels that help fuel and nurture tumor growth. But unlike most therapies aimed at tumor vasculature, the goal is not to destroy the cancer's blood supply.

"We don't want to kill tumor vessels," said senior author Jeffrey M. Arbeit, MD, professor of urologic surgery and of cell biology and physiology. "We want to hijack them and turn them into factories for producing molecules that alter the tumor microenvironment so that it no longer nurtures the tumor. This could stop the tumor growth itself or cooperate with standard chemotherapy and radiation to make them more effective. One advantage of this strategy is that it could be applied to nearly all of the most common cancers affecting patients."

In theory, Arbeit pointed out, this approach could be applied to diseases other than cancer in which the blood vessels are abnormal, including conditions like Alzheimer's disease, multiple sclerosis or heart failure.

The viral vector Curiel, Arbeit and their colleagues developed contains a section of DNA called ROBO4 known to be switched on in the cells lining blood vessels within tumors.

In mice, the researchers showed that they could inject the vector into the blood stream and that it accumulated in the tumor vasculature, largely avoiding the lung, kidney, heart and other healthy organs.

The researchers used the viral vectors to deliver a gene that simply caused cells lining the blood vessels to glow green so they could see whether the vectors gathered in the tumors and bypassed healthy areas.

These mice had tumors in the kidneys and cancerous kidney cells in the skin. In one case, the tumor in the mouse kidney spontaneously spread to an ovary. The investigators showed that the blood vessels feeding the metastatic tumors glowed green but not vessels in the normal part of the ovary.

Adding the anti-clotting drug warfarin also blocked the vector from gathering in the liver by blocking viral interactions with the body's blood-clotting machinery, according to the study. While the researchers say treating cancer patients with warfarin would not be feasible because of the bleeding risk, previous work from their group has shown genetic ways to manipulate the viral vector to prevent it from accumulating in the liver.

"We used a combination of targeting strategies," said Curiel. "We combined a method we had developed to detarget the liver and a method to target the blood vessels. This combination allowed us to inject the vector into the bloodstream of the mouse, where it avoided the liver and found the proliferative vessels of interest to us."



INFORMATION:

This work was funded by the National Institutes of Health (NIH) grant numbers R01CA159959 and R01CA154697.

Lu ZH, Kaliberov S, Sohn RE, Kaliberova L, Curiel DT, Arbeit JM. Transcriptional targeting of primary and metastatic tumor neovasculature by an adenoviral type 5 roundabout4 vector in mice. PLOS ONE. Dec. 23, 2013.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.



ELSE PRESS RELEASES FROM THIS DATE:

Children at lower risk for peanut, tree nut allergies if moms ate more nuts while pregnant

2013-12-27
Children at lower risk for peanut, tree nut allergies if moms ate more nuts while pregnant Children appear to be less at risk for developing peanut or tree nut (P/TN) allergies if their mothers are not allergic and ate more nuts during pregnancy, ...

Study examines inosine to increase urate levels in patients with Parkinson disease

2013-12-27
Study examines inosine to increase urate levels in patients with Parkinson disease The drug inosine appears to be a safe and effective way to raise blood and cerebrospinal fluid urate levels in patients with early Parkinson disease (PD), suggesting it may ...

Increase in consultations for Medicare patients before cataract surgery

2013-12-27
Increase in consultations for Medicare patients before cataract surgery Preoperative consultations before cataract surgery became more common for Medicare patients despite no clear guidelines about when to require such a service, hinting at unnecessary use of health ...

Mongooses synchronize births to escape despotic females

2013-12-27
Mongooses synchronize births to escape despotic females Some mammals may have evolved to synchronise births as a way of evading the threat of infanticide, according to a study led by the University of Exeter. To ensure groups remain productive, some ...

Breast cancer patients experience fewer side effects from anticancer drug when receiving acupuncture

2013-12-27
Breast cancer patients experience fewer side effects from anticancer drug when receiving acupuncture A new analysis has found that both real and sham acupuncture treatments may help alleviate side effects of drugs commonly used to treat breast cancer. Published early online in ...

Pregnant women need not avoid peanuts, evidence shows

2013-12-27
Pregnant women need not avoid peanuts, evidence shows Peanut and tree nut allergy incidence lower among children whose mothers ate them during pregnancy BOSTON (Dec. 23, 2013)—Women need not fear that eating peanuts during pregnancy could cause ...

Embargoed study: New quality, payment initiative positively impacts pediatric care

2013-12-27
Embargoed study: New quality, payment initiative positively impacts pediatric care Contracting model, based on global payment and pay-for-performance, improves quality of care for sickest pediatric patients BOSTON (Dec. 23, 2013)—Within two years ...

Preop testing for low-risk cataract surgery patients: Choosing wisely or low-value care? Penn Medicine

2013-12-27
Preop testing for low-risk cataract surgery patients: Choosing wisely or low-value care? Penn Medicine (PHILADELPHIA) – The elimination of extensive routine preoperative tests and consultations represents an area of ...

Getting excited helps with performance anxiety more than trying to calm down, study finds

2013-12-27
Getting excited helps with performance anxiety more than trying to calm down, study finds Simple statements about excitement could have big effects, research shows WASHINGTON – People who tell themselves to get excited rather than trying to relax ...

Library that can determine resistance

2013-12-27
Library that can determine resistance Genetic screening identifies genes driving resistance with a guide RNA library Researchers have developed a method to create a comprehensive library of mutations across all genes in the mouse genome. This library ...

LAST 30 PRESS RELEASES:

Signs identified that precede sudden arrhythmic death syndrome in young people

Discovery of bacteria's defence against viruses becomes a piece of the puzzle against resistance

Pre-eclampsia is associated with earlier onset and higher incidence of cardiovascular risk factors

Warwick astronomers discover doomed pair of spiralling stars on our cosmic doorstep

Soil conditions significantly increase rainfall in world’s megastorm hotspots

NK cells complexed with bispecific antibody yield high response rates in patients with lymphoma

Planetary health diet and mediterranean diet associated with similar survival and sustainability benefits

Singapore launches national standard to validate antimicrobial disinfectant products

Molecular stool test could improve detection of tuberculosis in adults with HIV

Suspected fibrocartilaginous embolus in Asian small-clawed otter (Aonyx cinereus)

Enhancing heat transfer using the turbulent flow of viscoelastic fluids

Exercise as an anti-ageing intervention to avoid detrimental impact of mental fatigue

UMass Amherst Nursing Professor Emerita honored as ‘Living Legend’

New guidelines aim to improve cystic fibrosis screening

Picky eaters by day, buffet by night: Butterfly, moth diets sync to plant aromas

Pennington Biomedical’s Dr. Leanne Redman honored with the E. V. McCollum Award from the American Society for Nutrition

CCNY physicists uncover electronic interactions mediated via spin waves

Researchers’ 3D-printing formula may transform future of foam

Nurture more important than nature for robotic hand

Drug-delivering aptamers target leukemia stem cells for one-two knockout punch

New study finds that over 95% of sponsored influencer posts on Twitter were not disclosed

New sea grant report helps great lakes fish farmers navigate aquaculture regulations

Strain “trick” improves perovskite solar cells’ efficiency

How GPS helps older drivers stay on the roads

Estrogen and progesterone stimulate the body to make opioids

Dancing with the cells – how acoustically levitating a diamond led to a breakthrough in biotech automation

Machine learning helps construct an evolutionary timeline of bacteria

Cellular regulator of mRNA vaccine revealed... offering new therapeutic options

Animal behavioral diversity at risk in the face of declining biodiversity

Finding their way: GPS ignites independence in older adult drivers

[Press-News.org] Gene therapy method targets tumor blood vessels