Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene Therapy "Trains" Immune System to Destroy Brain Cancer Cells

Study in laboratory rats, conducted at Cedars-Sinai Medical Center,
supports future translation to human trial

A new gene therapy approach that attracts and “trains” immune system cells to destroy deadly brain cancer cells also provides long-term immunity, produces no significant adverse effects and -- in the process of destroying the tumor -- promotes the return of normal brain function and behavioral skills, according to a study conducted by researchers at Cedars-Sinai Medical Center’s Board of Governors Gene Therapeutics Research Institute.

The study was conducted in a recently developed laboratory rat model of glioblastoma multiforme (GBM) that closely simulates outcomes in humans and supports the translation of this procedure to human clinical trials later this year. Results of the study are described in the Feb. 19 issue of Molecular Therapy, the journal of the American Society for Gene Therapy.

“These findings appear to be a significant milestone in creating an effective treatment for glioblastoma multiforme,” said Maria Castro, Ph.D., co-director of the Board of Governors Gene Therapeutic Research Institute and principal investigator of the study. “This therapy significantly improved survival rate, induced long-lasting systemic anti-tumor immunity, and resolved the neuropathological abnormalities caused by the tumors, which has been a stumbling block to many promising treatments.”

The article documents the gene therapy’s effectiveness in killing GBM cells and launching an effective and sustained systemic immune response. It also focuses on the safety of the therapy as well as its ability to restore normal brain function and reverse behavioral deficits caused by large tumors.

Humans with GBM often suffer behavioral abnormalities that affect concentration, memory and balance. In the animal studies, rats exhibited abnormal rotational movements. The research team found that as the tumors grew, they displaced and compressed nerve terminals and impulse-conducting axons. But long-term survivors who had received the gene therapy did not have long-term injury or behavioral impairment resulting from the tumor or the treatment.

“Tumor growth causes behavioral deficits, but even treatments, such as chemotherapy and radiation therapy, can cause learning disabilities and other cognitive problems. In our animal study, this therapy eliminated the tumor mass and reversed the deficits that were caused by the tumor,” said Pedro Lowenstein, M.D., Ph.D., co-principal investigator on the study and director of the Board of Governors Gene Therapeutics Research Institute.

Glioblastoma multiforme, the most common and deadly type of brain cancer, usually claims the lives of victims within six to 12 months of diagnosis. It is extremely difficult to treat for a variety of reasons. GBM tumors grow rapidly, often becoming large before a diagnosis is made. Also, cells readily infiltrate neighboring tissue and migrate to other areas, hampering complete surgical removal. Chemotherapy and radiation therapy are unable to eliminate all residual GBM cells, which frequently become resistant to the treatments.

The blood-brain barrier also prevents chemotherapy from effectively reaching tumor cells, and key cells needed to launch and sustain a systemic anti-tumor immune response – dendritic cells, or antigen-presenting cells – do not naturally occur within the brain.

The gene therapy approach developed at Cedars-Sinai sidesteps all of these challenges. The researchers used a virus stripped of its disease-causing genes as a vehicle to deliver two therapeutic proteins directly into the tumor cells. One protein, FMS like tyrosine kinase 3 ligand (Flt3L), drew dendritic cells into the brain. Another protein, herpes simplex virus type 1 thimidine kinase (HSV1-TK), combined with the antiviral gancyclovir (GCV), killed tumor cells.

Dendritic cells clean up debris from dying cells and in the process alert immune system cells of the existence of foreign entities, or antigens – in this case, GBM cells. Newly “educated” immune system cells then swarm to the tumor cells to destroy them.

In an earlier study, the Cedars-Sinai researchers used HSV1-TK and GCV alone to treat GBM and found that about 20 percent of the animals survived, compared to controls. By adding the dendritic-cell inducing Flt3L, the survival rate jumped to about 70 percent. Systemic immune activity was sustained, even fending off a “re-challenge” with additional tumor cells. In this study, the researchers at the BOG-GTRI reported that this therapy could also revert behavioral abnormalities caused by the growing tumor in the brain.

“In the fairly near future, this combined gene therapy may work synergistically with current therapies, including chemotherapy and radiation therapy, allowing doctors to reduce dosages and avoid side effects,” Dr. Castro said. “But with the safety, effectiveness and curative potential seen in these studies, we are hopeful that gene therapy for GBM could become the new standard of care.”

The study was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke, The Bram and Elaine Goldsmith and the Medallions Group Endowed Chairs in Gene Therapeutics, the Linda Tallen & David Paul Kane Foundation Annual Fellowship, and the Board of Governors at Cedars-Sinai.

Citation: Cancer Research, Combined immune-stimulation and conditional cytoxic gene therapy provide long term survival in a large glioma model (August 2005).

Simi Singer | Cedars-Sinai Medical Center
Further information:

Further reports about: GBM Governors Treatment behavioral immune therapeutic therapy tumor cells

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>