Apr. 18, 2007 Researchers in Germany have hidden vaccine-grade measles virus inside artificially generated blood cells in order to devise a search-and-destroy therapy for human brain cancer that can't be "seen" by the immune system.
They say their mouse experiments show a proof of principle that this non-pathogenic virus can attack glioma by getting inside tumor cells and replicating, destroying the common brain tumors from the inside out. This and other so-called "oncolytic" viruses are already being tested in clinical trials, but their effectiveness has been limited by an immediate human immune response, the researchers say.
"In an immune-competent patient, the immune system will fight the virus, and most adults are immune against measles since they have been vaccinated against the disease in childhood or have had measles," said Christian Beltinger, M.D., an associate professor at the University Children's Hospital in Ulm. "Although cancer patients are immune-compromised by their disease or because of therapy, they still may mount a sufficient attack against vaccine measles virus."
To trick this immune surveillance, the researchers generated blood outgrowth endothelial cells (BOECs), which are produced outside of the body using human blood bathed in a cocktail of growth factors. "They do not naturally occur in the blood, but they are derived from endothelial progenitor cells, rare cells that are produced in the bone marrow and shed into the blood," Dr. Beltinger said.
These cells are well suited for cancer therapy for two reasons, he said. If a vaccine measles virus is tucked within them, it can't be reached by the immune system's neutralizing antibodies. Also, they are endothelial progenitor cells, which are recruited in the body wherever new blood vessels are formed.
"Tumors need vessels to grow, hence they recruit these blood progenitor cells," Dr. Beltinger said. "That makes them home to the tumors."
BOECs have been used for other gene therapeutic approaches, such as for hemophilia, but this is the first time they have been adapted to carry vaccine measles virus, he said.
To test how well they functioned as a cancer therapy, the researchers injected U87 cells (the most commonly used human glioma cancer cell line) into the brains of immune-compromised mice. Once the tumors were established, BOECs recently infected with vaccine measles virus were injected around, but not into, the brain tumor. These loaded blood cells navigated through normal brain tissue to the tumor mass, and once inside, the BOECs released the virus into surrounding tumor cells. It then spread to other tumor cells.
Eventually the blood cells died. This delay of death, however, was sufficient to allow the infected cells to home to the tumor and release the virus, the researchers say.
They found that mice treated with BOECs survived significantly longer than mice receiving just empty blood cells or "naked" measles virus. But the researchers say that all mice eventually died, showing that the therapy could not completely eradicate the tumors.
"While these modified blood cells carrying vaccine measles virus look like a promising novel therapy for gliomas, it is still a preclinical experimental approach," Dr. Beltinger said. "Potentially it could be used on most malignant gliomas, including glioblastomas, because the targeting of the virus can be genetically modified."
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