Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein delivered via genetically engineered virus slowed glioblasoma multiforme growth

07.12.2004


Despite aggressive treatment, glioblastoma multiforme (GBM) – the most common and deadly of brain cancers – usually claims the lives of its victims within six to 12 months of diagnosis. This statistic has changed little over the years, largely because the cancer grows so quickly that neither surgery, radiation, or chemotherapy can stop it.



Now, researchers at Cedars-Sinai Medical Center have found that a small protein called hsFlt3L delivered via a genetically engineered virus increased the number of immune cells in the brain and significantly slowed tumor growth, increasing the survival of laboratory rats in pre-clinical studies. The study, published in the December issue of the journal, Molecular Therapy, may lead to a new way to treat patients with GBM. "Importantly, our study is the first to show that GBM tumors shrank or were completely eliminated in lab rats, which is likely due to the ability of the protein, hsFlt3L to stimulate the production of fully mature immune cells within the brain," said Maria Castro, Ph.D., co-director of the Gene Therapeutics Research Institute at Cedars-Sinai Medical Center and the senior author of the study. "Since gene therapy has given us the tool to deliver this protein, our hope is to translate these laboratory studies into clinical trials in patients with GBM."

GBM tumors develop in the supportive tissue of the brain and grow quickly, often becoming very large before a person experiences symptoms and is diagnosed. Surgery is typically performed to remove as much of the tumor as possible and followed with radiation and/or chemotherapy to slow progression of the disease. But despite aggressive treatment, the tumor recurs and patients usually die within a year’s time. Because GBM is so aggressive, the disease has been the target of a number of laboratory studies and clinical trials investigating the effectiveness of gene therapy to deliver novel therapeutic agents to the brain. Most of these have investigated the use of the suicide gene from the herpes simplex virus to develop a gene therapy approach that kills cancer cells, in the presence of the antiviral drug, gancyclovir. In laboratory studies, this type of gene therapy has proved almost 100 percent effective. But in clinical trials, it has had limited effectiveness, suggesting that the virus is not able to deliver the suicide gene effectively into a large tumor mass. "Importantly, results from these studies showed us that gene therapy was safe, but that we needed to design a viral vector that would harness the power of the immune system to help eliminate the tumor," commented Dr. Castro.


Genetically engineered viruses are used to transport genes and/or proteins into cells and have been used in gene therapy research for the last ten years. Just like a viral infection, they work by tricking cells into accepting them as part of their own genetic coding. To make them safe, scientists remove the genetic viral genes that cause infection and engineer them so that they stop reproducing and also carry therapeutic genes. In this study, researchers from the "Gene Therapeutics Research Institute" team, led by Drs. Castro and Pedro Lowenstein, investigated the effectiveness of an anti-brain tumor therapy using hsFlt3L, a protein that has a unique ability to increase the number of immune cells when delivered into the brain. Specifically, these immune cells are called dendritic cells and work by presenting antigens – or foreign invaders that enter the body – and inducing the generation of cell-killing T-lymphocytes. Because the brain lacks dendritic cells and is protected by the blood brain barrier, the investigators tested an adenoviral vector that had been genetically manipulated to selectively express hsFlt3L to find out if it would increase the number of dendritic cells in the brain of laboratory rats with GBM.

To evaluate whether hsFlt3L could shrink brain tumors and prolong survival, rats with GBM were injected with increasing doses of the engineered virus expressing hsFlt3L or a saline placebo that was used as a control. The investigators found that 70 percent of the rats treated with hsFlt3L survived long-term, for over a year, when the higher dose was used, and that it did not cause adverse immune reactions in the normal brain. In contrast, the rats treated with placebo substances died from their tumors within one week after the start of the treatment. "Taking into account both the effectiveness of the treatment in the preclinical GBM animal model and also the lack of overt adverse side effects to the surrounding normal brain, we hope to start clinical trials using this combined immune and suicide gene therapy approach within the next three years," said Dr Castro.

Among rats treated with hsFlt3L, the investigators found that 33 percent were completely tumor free at three months, while all those who survived for six months or longer had no tumors at all. Moreover, no rats died between the three and six months’ time points. "These results show that tumor growth was greatly inhibited in rats treated with hsFlt3L and reflect an ongoing battle between the tumor and the immune system," said Dr. Castro. "In other words, hsFlt3L stimulated an immune response as evidenced by an increase in the number of dendritic cells in the brain and led to complete elimination of the tumor in most of the rats, while slowing down tumor growth in the others. The combined data presented has important implications for using immunotherapy to treat brain tumors in patients with GBM."

Kelli Hanley | EurekAlert!
Further information:
http://www.cshs.org

More articles from Studies and Analyses:

nachricht Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>