Mayo Clinic Cancer Center has opened a new clinical study using a vaccine strain of the measles virus to attack recurrent glioblastoma multiforme, a largely untreatable brain tumor. This is the second of several pending molecular medicine studies in patients using measles to kill cancer.
"We are looking at better ways to treat some of the most lethal cancers," says Eva Galanis, M.D., oncologist and lead researcher on the glioblastoma multiforme project in the measles virus investigation. "We have shown in the laboratory and in several animal models that measles virus strains can significantly shrink glioma tumors and prolong animal survival. It is very rewarding to see this work maturing to the point of now being able to offer this novel and promising treatment approach to patients with recurrent glioblastoma multiforme." She also reports that toxicology studies, conducted in conjunction with Federal Drug Administration, showed an excellent safety profile.
Mayo Clinic is unique in its pursuit of oncolytic measles vaccine strains for cancer treatment, and the research has grown from the most basic laboratory science to the sophisticated therapy being tested today in several tumor types, including glioblastoma multiforme, recurrent ovarian cancer and multiple myeloma.
Many cancer cells, including glioblastoma cells, overexpress a specific protein, CD46, which allows tumor cells to evade destruction by the immune system. Strains of the measles virus, including the one in this study, seek out this protein, entering the glioblastoma multiforme tumor. Upon entry, the virus begins to spread, infecting nearby tumor cells and fusing them, which augments the effect of infection and increases cancer cell death.
Mayo's research team has an ongoing clinical study for ovarian cancer. "We've seen early evidence of biologic activity," says Dr. Galanis. "The ovarian cancer trial, though in its early stages, has demonstrated safety, which now allows administration of higher and potentially even more potent viral doses."
The glioblastoma multiforme study, which opened today, is designed to test the safety of the virus for the treatment of gliomas and enable biological monitoring of anti-tumor activity.
"The measles virus we are using in the glioblastoma multiforme trial provides a noninvasive way to monitor viral effects in the tumor," says Dr. Galanis. "When the virus replicates, it produces a marker protein that we can detect in the blood using a clinically-available assay. Repeat brain tumor biopsies for this purpose are not always safe or ethically justified. Instead we can monitor viral propagation in the tumor with a blood test, allowing us to adjust the dosage to increase the likelihood of therapeutic benefit."
Eligible candidates for the therapy will have glioblastoma multiforme that has progressed after surgery and radiation therapy, and be candidates for surgery. They also must be immune to measles, either having had the disease or been vaccinated against it.
In the 1970s, measles infections were observed to cause regression of pre-existing cancer tumors in children. This information was noted, but nothing was done to study this phenomenon until the late 1990s, when under the direction of Stephen Russell, M.D., Ph.D., Mayo Clinic Cancer Center's Molecular Medicine Program began looking into it, resulting in the current study and other related projects.
"Mayo is the perfect place to develop a therapeutic virus because you need a wide range of expertise," says Dr. Russell. "From basic scientists who create and test the vaccine strain to those who determine the best way to manufacture a safe biological delivery mechanism, and finally, to clinicians who understand the science and develop guidelines by which the study is conducted and correctly carried out, our team is one of the best. Everything we do focuses on achieving the greatest benefit for the patient."
Later this fall, Dr. Russell's team plans to open a clinical study to test the effectiveness of another version of the measles virus on multiple myeloma. The researchers also are looking at ways to use the measles virus to combat breast and pancreatic cancer.
The glioblastoma multiforme research that led to the clinical trial was conducted within Mayo Clinic Cancer Center's Specialized Program of Research Excellence (SPORE) that focuses on the brain. SPORE programs are highly competitive research initiatives funded by the National Cancer Institute (NCI) to develop novel approaches to cancer therapy and to translate basic science into clinical application. Mayo conducts research under five other SPOREs, including breast, pancreatic and prostate cancers, as well as lymphoma and myeloma.
Funding for the full measles virus investigation came from the brain SPORE program and other NCI funds as well as the Harold W. Siebens Foundation, the Commonwealth Cancer Foundation, the George M. Eisenberg Foundation, the Donaldson Charitable Trust and a Fraternal Order of Eagles Grant. Other Mayo Clinic Cancer Center researchers participating in the glioblastoma multiforme project include Jan Buckner, M.D.; Fredric Meyer, M.D.; Corey Raffel, M.D., Ph.D.; Brian O'Neill, M.D.; Matthew Maurer; and Mark Federspiel, Ph.D.
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