Gene therapy technique thwarts cancer by cutting off tumor blood supplyJune 12, 2009University of Florida researchers have come up with a new gene therapy method to disrupt cancer growth by using a synthetic protein to induce blood clotting that cuts off a tumor's blood and nutrient supply. In mice implanted with human colorectal cancer cells, tumor volume decreased 53 percent and cancer cell growth slowed by 49 percent in those treated with a gene that encodes for the artificial protein, compared with those that were untreated. The research team, led by Dr. Bradley S. Fletcher, an assistant professor of pharmacology and therapeutics in the College of Medicine, created the so-called fusion protein to target another protein called tumor endothelial marker 8, or TEM8, which was recently found to be preferentially expressed in the inner lining of tumor vessels. Such differences in protein expression enable delivery of drug molecules to the cells that harbor these proteins. "The protein we created did a very good job of homing to the tumor and binding," said Stephen Fernando, who recently completed his doctoral studies. "By targeting TEM8, we can potentially create a therapy against cancer." The Fletcher group is the first to target cancer cells through protein binding to TEM8. The findings, now available online, are featured on the cover of the June 15 edition of Cancer Research. "If you can cut off the blood supply, then you can inhibit the tumor from growing -- there have been many attempts," said Brad St. Croix, director of the National Cancer Institute's Tumor Angiogenesis Section, whose group first identified the TEM genes that over-express in tumor endothelial cells. "The concept of targeting tumor blood vessels has been around for many years, but it's good that we're finally getting around to the stage where we can see the vessels being targeted therapeutically -- it's pretty exciting, I think." St. Croix was not part of the current research team, but donated some experimental materials. The UF group created a "fusion protein" -- part of which binds to TEM8, and the other which promotes thrombosis, or blood clotting -- and delivered genes that encode for it to the lungs of mice. The delivery vehicle was a transposon called Sleeping Beauty, a piece of DNA that can insert new genes stably and efficiently into a cell's genome. The lungs then functioned as a factory to produce the protein that later found its way to the target cells in the tumor vessels. "We felt that TEM8 was an ideal target because it was inside the vessel, preferentially expressed there and unique," Fletcher said. In addition to promoting blood clots, the strategy also resulted in reduced tumor vessel density, possibly by interfering with TEM8 function. Fletcher's group previously applied the Sleeping Beauty transposon gene delivery method to the treatment of hemophilia and pulmonary hypertension and the prevention of lung transplant rejection in animal studies. After developing those three successful models, they looked for disease applications in which poor outcomes would be worth the risk associated with gene therapy. "We felt that cancer was potentially a target," Fletcher said. "Gene therapy has a lot of risk associated with it, so you don't want to do it for diseases that are not life-threatening." The group plans to come up with a method to increase the amounts of the thrombosis-inducing protein produced in the body, and test whether higher dosing leads to unintended blood clots. They are also looking into ways to deliver the protein directly to the sites of interest, rather than through genes that later produce the protein, and apply the method in other areas such as prostate cancer. Other work will include the use of coated nanoparticles to detect tumors and deliver drugs or radiate heat to destroy cancer cells when bombarded by radio waves. University of Florida |
|||||||||||||||||||||
| Related Gene Therapy Current Events and Gene Therapy News Articles Research reveals lipids' unexpected role in triggering death of brain cells The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators. No-entry zones for AIDS virus The AIDS virus inserts its genetic material into the genome of the infected cell. Scientists of the German Cancer Research Center have now shown for the first time that the virus almost entirely spares particular sites in the human genetic material in this process. This finding may be useful for developing new, specific AIDS drugs. Cornell researchers identify a weak link in cancer cell armor The seeming invincibility of cancerous tumors may be crumbling, thanks to a promising new gene therapy that eliminates the ability of certain cells to repair themselves. Treatment to improve degenerating muscle gains strength A study appearing in Science Translational Medicine puts scientists one step closer to clinical trials to test a gene delivery strategy to improve muscle mass and function in patients with certain degenerative muscle disorders. Iowa State University researcher discovers key to vital DNA, protein interaction A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances." Scientists successfully reprogram blood cells Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome. Immune therapy can protect against or treat later lymphoma Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection. Caltech researchers show efficacy of gene therapy in mouse models of Huntington's disease Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington's disease in a variety of mouse models. Immunotherapy demonstrates long-term success in treating lymphoma Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT). Toward bold new anti-cancer medicines Bold new strategies in the battle against cancer may turn forms of the disease that presently are incurable into manageable conditions that can be controlled for long periods of time. More Gene Therapy Current Events and Gene Therapy News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||