Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel gene therapy for bladder cancer shows strong results in animal studies

08.09.2004


Novel Gene Therapy for Bladder Cancer Shows Strong Results in Animal Studies HOUSTON - Gene therapy that causes the bladder to act like a "bioreactor" to produce and secrete the anti-cancer agent interferon-alpha has shown dramatic benefits in preclinical tests, say researchers at The University of Texas M. D. Anderson Cancer Center.



The researchers say their findings, published in the September issue of Molecular Therapy, suggest this gene therapy strategy holds much promise for treating aggressive human superficial bladder cancer and that a clinical trial is being planned.

Human bladder tumors growing in experimental mice substantially decreased in size after two treatments with novel gene-based therapy. There was little or no evidence of cancer cells remaining in the bladder in many of the mice after treatment. Also, every kind of bladder cancer cell line tested in the laboratory responded, even cells known to be resistant to the interferon-alpha protein. "Of course these results have been achieved in mice, not humans, but they are very exciting," says the lead investigator William Benedict, M.D., professor in the Department of Genitourinary Medical Oncology. "I have never seen a potential therapy for superficial bladder cancer that could produce such marked regression of tumors within the bladder."


Bladder cancer is the fifth leading U.S. cancer, and "superficial" bladder cancer - cancer confined to the lining of the bladder wall - is the most common type, with more than 45,000 new cases each year. Although some patients with this cancer can be cured with the standard biologic therapy, the use of BCG, tumors will reappear in about half of patients, and up to 30 percent of them will die from disease. Because neither BCG nor chemotherapy can effectively prevent a significant percentage of superficial bladder cancer from becoming aggressive, researchers at M. D. Anderson have been studying novel gene therapy approaches to this clinical problem. Their work is being funded by a $13 million Specialized Programs of Research Excellence (SPORE) grant awarded to M. D. Anderson by the National Cancer Institute in 2001 - the only such federal SPORE dedicated to bladder research.

The bladder has long been thought to be ideal target for gene therapy, because it is easily accessible by catheter, and is largely a self-contained "bag-like" organ. Benedict and his team of researchers decided to look at use of gene therapy to deliver interferon-alpha, an immune system modulator which can improve a patient’s natural response against cancer as well as kill cancer cells directly. Interferon-alpha is commonly used as treatment in a number of cancers, such as several types of leukemias, lymphoma, melanoma, and kidney cancer. However, it has been observed that tumor cells can become resistant to the immune protein.

To investigate alternative ways to deliver interferon, the researchers teamed up with scientists from the San Diego biotechnology company Canji, Inc., which is affiliated with Schering-Plough Corporation, to evaluate recombinant adenoviruses encoding interferon-alpha (Ad-IFN_). These modified adenoviruses can produce high levels of interferon-alpha when they infect cells, but are engineered to prevent virus replication. The investigators combined Ad-IFN_ with an additional agent, Syn3, to enhance expression of IFN in the cells which line the inside of the bladder.

Mice that were growing human tumors in their bladders received two one-hour instillations directly into the bladder. The cells lining the inside of the bladder, both normal and cancerous, "took up" the Ad-IFN_, and a marked decrease in tumor size was seen. "This is a major finding since many human bladder cancer cell lines are resistant to the interferon-alpha protein, including the ones used in this study," says Benedict. "In addition, there was little apparent toxicity."

One of the key advances is that the virus was able to harness cells in the bladder to function as "biological factories, producing high local concentrations of interferon-alpha in the bladder over an extended time," he says. "That has never been seen before." "The degree of effectiveness of the Ad-IFN_/Syn3 therapy was a surprise to all of us," says Benedict. "We know that going from mouse to man is a crucial step, but if the therapy performs half as well in the clinic as in this preclinical study, we may well significantly advance the care of patients with bladder cancer."

Heather Russell | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>