ROCHESTER, Minn. -- A Mayo Clinic research team has devised a new virus-based
gene therapy delivery system to help fight cancer. Researchers say their findings
will help overcome hurdles that have hindered gene therapy cancer treatments.
The Mayo research team, which includes a collaborator
from the United Kingdom, describes its new approach
in the current edition of Nature Medicine ( http://www.nature.com/nm/index.html) .
approach relies on "therapeutic hitchhikers" --
particles derived from retroviruses (RNA-containing
viruses that incorporate into the genomes of infected
cells and then produce a therapeutic gene). The viral
particles attach to a specific kind of T cell in
the immune system and "hitchhike" to the tumor because
T cells home in on tumors naturally; T cells are
the immune system's major line of defense against
tumors. By hitching a ride on the T cells, the therapeutic
particles can hit their tumor target while avoiding
detection (and destruction) by the immune system.
When the Mayo team experimented with the hitchhiking
approach in mice using human and mouse cancer cells,
they observed significant cure rates of metastatic
-- or spreading -- tumors.
"Any clinical situation in which cells home to disease
sites -- such as inflammation or autoimmune disease
-- might benefit from this approach," explains Richard
Vile, Ph.D., Mayo Clinic molecular immunologist and
lead researcher of the investigation. "Our work is
an important contribution to the maturation of the
field of gene therapy because ultimately treating
cancers by gene therapy depends on scientists' ability
to specifically target tumor cells in the patient
-- and this specific-delivery feature has eluded
researchers for a variety of reasons. But by devising
a way for viruses to hitch rides on antigen-specific
T cells, we've been able to get over multiple obstacles
to gene therapy."
Dr. Vile emphasizes that the work is still experimental
and not yet ready for use in human patients. But
if larger studies validate these findings, the therapeutic
hitchhiker approach may be employed in clinical trials
of new treatments.
Significance of the Mayo Research
The Mayo investigators have invented a simpler method
for using modified viruses to transport therapeutic
genes to tumors. They are the first to exploit traits
of retroviruses during the infection process of a
cell in which attachment to the cell can occur in
a nonspecific way. This opens up new opportunities
for using viruses therapeutically because this method
of attachment allows researchers not only to target
particular cells, but also to more easily gain entry
into the cells -- which they must do to deliver therapeutic
genes to destroy tumors. The T cells also help kill
About the Investigation
Using mice, the Mayo Clinic team showed that retrovirus
particles could successfully attach to the surface
of primary T cells and then safely hitchhike -- be
carried through the bodies of mice that had fully
functioning immune systems and evade detection by
the immune system -- to reach tumors, the sites of
T cell accumulation. They further showed that once
it reached the tumor, the viral transporter successfully
transferred a gene to both mouse and human tumor
cells that then infected the cells. This proved that
the concept works.
Collaboration and Support
In addition to Dr. Vile, the Mayo Clinic research
team included Caroline Cole, Ph.D.; Jian Qiao, M.D.,
Ph.D.; Timothy Kottke; Rosa Maria Diaz, Ph.D.; Atique
Ahmed; Luis Sanchez-Perez; Gregory Brunn, Ph.D.;
and Jill Thompson. John Chester, M.B.B.S., Ph.D.,
collaborated from the Cancer Research UK Clinical
Center, St. James' University Hospital, Leeds, UK.
The work was supported by
MayoClinic.com ( http://www.mayoclinic.com )
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For more on Mayo Clinic research, go to http://www.mayo.edu .