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 Cells communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>