Florida: University of Florida Health researchers have discovered that a rabbit virus can deliver a one-two punch, killing some kinds of cancer cells while eliminating a common and dangerous complication of bone marrow transplants. For patients with blood cancers such as leukemia and multiple myeloma, a bone marrow transplant can be both curative and perilous. It replenishes marrow lost to disease or chemotherapy but raises the risk that newly transplanted white blood cells will attack the recipient’s body. Now researchers say the myxoma virus, found in rabbits, can do double duty, quelling the unwanted side effects of a bone marrow transplant and destroying cancer cells.
The virus could be especially helpful to patients who have recurring
cancer but cannot find a suitable bone marrow donor, said Christopher R.
Cogle, M.D., the study’s lead investigator and an associate professor
in the UF College of Medicine’s division of hematology and oncology.
Bone marrow transplants from partially matched donors carry about an 80
percent risk of graft-versus-host disease, and the myxoma treatment
would address that, Cogle said.
The myxoma virus also could improve bone marrow transplant options
among African-Americans and the elderly. Those patients are less likely
to find fully matched bone marrow donors, which raises the risk of
graft-versus-host disease, according to Cogle.
“Myxoma is one of the best strategies because it is effective but doesn’t affect normal stem cells,” he said.
During laboratory testing on human cells, the process worked this
way: The myxoma virus is attached to a type of white blood cell known as
a T-cell. The virus-laden white blood cells can then be delivered as
part of a bone marrow transplant from a donor. That’s when the virus
gets activated and goes to work. It blocks graft-versus-host disease, a
complication of bone marrow transplants that can cause problems
including skin rash, shortness of breath, abdominal pain, jaundice and
muscle weakness. In severe cases, these complications can be fatal. The
white blood cells then deliver the myxoma virus to cancer cells, which
are killed off by the virus.
The findings were published in the April 22 edition of the journal
Blood. After successfully testing the process with human cells,
researchers are now studying its effectiveness in a mouse model.
The dual action of the myxoma virus is particularly encouraging, said
Grant McFadden, Ph.D., a professor in the UF College of Medicine
department of molecular genetics and microbiology. It’s the first time
that a virus has been shown to simultaneously prevent graft-versus-host
disease and kill cancer cells in the laboratory, McFadden said.
The process is known to work on blood-related disorders such as
multiple myeloma and acute myeloid leukemia but could someday have
broader application for other kinds of cancer, he said. The myxoma virus
originates among rabbits in Australia and parts of Europe and is benign
The discovery might never have happened if not for a chance meeting
at a coffee kiosk on the health campus. Cogle and McFadden introduced
themselves to each other, which led to a collaboration that has lasted
“It’s one of the benefits of a health research campus like UF,” Cogle
said. “His virus killed the cancer cells that I grew in my lab and
spared normal blood stem cells.”
Another crucial part of the research team’s work was done by Nancy
Villa, Ph.D., a research scientist in the division of hematology and
oncology. Villa’s findings were crucial to understanding and explaining
how myxoma prevents graft-versus-host disease, Cogle said. McFadden
credits Villa for finding a way to explain to other scientists how the
virus-laden white blood cells can prevent graft-versus-host disease and
still be an effective killer of cancer cells. That knowledge will be
crucial as the team presses on with its research, McFadden said.
After the initial success with human cells, McFadden is cautiously
optimistic that a clinical trial could begin within a year. Before that,
researchers need to develop a clinical-grade virus, do safety testing
and raise about $1 million for clinical trials. The UF-owned patent on
the myxoma process has been licensed to a Houston-based company, which
will seek to raise money for clinical trials, Cogle said.
The research was supported by grants of $1.5 million each from the
Florida Bankhead-Coley Cancer Research Program and the National
Institutes of Health/National Cancer Institute. Additional financial
support came from the Gatorade Trust, which is administered by the
department of medicine and the UF Research Foundation.