Thema: Presse: A virus for the brain
Presse: A virus for the brain
Katja[a]
12.08.2004 12:56:52
News-Medical.Net World´s first gene therapy trial aimed at preventing cancer
...
A virus for the brain
The old saw goes that if curing cancer in mice was the same as curing it in humans, we would have won the war on cancer a long time ago.
While the point is taken, researchers at M. D. Anderson who last year cured brain cancer in mice were amazed because no one had ever before tested a drug that had any effect on malignant glioma, the most deadly of brain cancers.
Testing a gene therapy in mice, likened to a "viral smart bomb," the M. D. Anderson scientists found only empty cavities and scar tissue where human glioma tumors had once been. The therapy, known as Delta-24-RGD, had moved like waves throughout the brains of the mice, killing the cancer while leaving normal tissue intact.
While the treatment employs an adenovirus, it does not seem to produce toxic effects in the brain, say researchers. In fact, the mice tested were considered clinically cured of their brain tumors with little known side effects.
These animal tests, reported last year, were considered so promising that the National Cancer Institute moved immediately to produce, in its own labs, a clinical-grade version of the therapy, and scientists with the FDA began collaborating.
"We´ve never seen this kind of response before with any other treatment tested in either animals or humans," says the lead author of that study, Juan Fueyo, M.D., an assistant professor in the Department of Neuro-Oncology.
"Biologic viral therapy like this may be just what we need to treat a complex disease like cancer," says co-author Frederick Lang, M.D., an associate professor in the Department of Neurosurgery when the study was published. "Cancer can be devious in that it does everything possible to evade destruction. But viruses are equally tricky in their quest to invade cells and propagate."
Now, Delta-24-RGD is expected to start the first phase of human testing in late summer 2004, with a two-staged clinical trial of 15 patients each. One stage will offer the treatment by injection to patients with recurrent gliomas who cannot be treated with surgery. Progress will be monitored with serial diagnostic scans. In the second stage, patients with a glioma will have the therapy, followed by surgery two weeks later. The excised tumor will be examined to see if it has been damaged.
This trial is just part of an ongoing larger "platform" of research that is continually refining Delta-24-RGD therapy, says Charles Conrad, M.D., an associate professor in the Department of Neuro-Oncology who works with Fueyo, Lang and others on the "Delta team."
They have already created a second and now a third generation of the therapy, each of which is proving more adept in infecting cancer cells and disarming them. One idea is to insert genes into the viral smart bomb that will switch on chemotherapy drugs. This way, a patient could receive an inert form of a chemotherapy drug that would be non-toxic to normal cells, but would be activated by the Delta virus when it spreads in cancer cells. "We would deliver the gene that activates the chemotherapy drug only to tumor cells," says Conrad.
The team, which includes other international and national investigators, also is exploring adapting Delta-24-RGD to other cancer types, such as colon cancer. Questions remain, however, as to whether the therapy will evoke a systemic immune response and just how the virus will be able to spread given physical barriers - such as bones or cavities - that are just a natural part of the body´s interior. Many solid tumors also contain areas of dead tissue, which could stop the virus´s ability to replicate. Finally, researchers are concerned about the issue that has dogged all adenovirus vectors - that, below the neck as it were, a patient could mount an immune response that would blunt the effectiveness of the therapeutic virus.
"We will have our proof of principle in treating gliomas," says Conrad. "If it is safe, and shows some benefit, we will want to try it in other cancers."
Posted By: News-Medical in Disease News
Published: Wednesday, 5-May-2004
...
A virus for the brain
The old saw goes that if curing cancer in mice was the same as curing it in humans, we would have won the war on cancer a long time ago.
While the point is taken, researchers at M. D. Anderson who last year cured brain cancer in mice were amazed because no one had ever before tested a drug that had any effect on malignant glioma, the most deadly of brain cancers.
Testing a gene therapy in mice, likened to a "viral smart bomb," the M. D. Anderson scientists found only empty cavities and scar tissue where human glioma tumors had once been. The therapy, known as Delta-24-RGD, had moved like waves throughout the brains of the mice, killing the cancer while leaving normal tissue intact.
While the treatment employs an adenovirus, it does not seem to produce toxic effects in the brain, say researchers. In fact, the mice tested were considered clinically cured of their brain tumors with little known side effects.
These animal tests, reported last year, were considered so promising that the National Cancer Institute moved immediately to produce, in its own labs, a clinical-grade version of the therapy, and scientists with the FDA began collaborating.
"We´ve never seen this kind of response before with any other treatment tested in either animals or humans," says the lead author of that study, Juan Fueyo, M.D., an assistant professor in the Department of Neuro-Oncology.
"Biologic viral therapy like this may be just what we need to treat a complex disease like cancer," says co-author Frederick Lang, M.D., an associate professor in the Department of Neurosurgery when the study was published. "Cancer can be devious in that it does everything possible to evade destruction. But viruses are equally tricky in their quest to invade cells and propagate."
Now, Delta-24-RGD is expected to start the first phase of human testing in late summer 2004, with a two-staged clinical trial of 15 patients each. One stage will offer the treatment by injection to patients with recurrent gliomas who cannot be treated with surgery. Progress will be monitored with serial diagnostic scans. In the second stage, patients with a glioma will have the therapy, followed by surgery two weeks later. The excised tumor will be examined to see if it has been damaged.
This trial is just part of an ongoing larger "platform" of research that is continually refining Delta-24-RGD therapy, says Charles Conrad, M.D., an associate professor in the Department of Neuro-Oncology who works with Fueyo, Lang and others on the "Delta team."
They have already created a second and now a third generation of the therapy, each of which is proving more adept in infecting cancer cells and disarming them. One idea is to insert genes into the viral smart bomb that will switch on chemotherapy drugs. This way, a patient could receive an inert form of a chemotherapy drug that would be non-toxic to normal cells, but would be activated by the Delta virus when it spreads in cancer cells. "We would deliver the gene that activates the chemotherapy drug only to tumor cells," says Conrad.
The team, which includes other international and national investigators, also is exploring adapting Delta-24-RGD to other cancer types, such as colon cancer. Questions remain, however, as to whether the therapy will evoke a systemic immune response and just how the virus will be able to spread given physical barriers - such as bones or cavities - that are just a natural part of the body´s interior. Many solid tumors also contain areas of dead tissue, which could stop the virus´s ability to replicate. Finally, researchers are concerned about the issue that has dogged all adenovirus vectors - that, below the neck as it were, a patient could mount an immune response that would blunt the effectiveness of the therapeutic virus.
"We will have our proof of principle in treating gliomas," says Conrad. "If it is safe, and shows some benefit, we will want to try it in other cancers."
Posted By: News-Medical in Disease News
Published: Wednesday, 5-May-2004
Katja[a]
