ScienceDaily (Dec. 18, 2007) --  An international team of researchers
led by Mayo Clinic have designed a technique that uses the body's own
cells and a virus to destroy cancer cells that spread from primary
tumors to other parts of the body through the lymphatic system. In
addition, their study shows that this technology could be the basis
for a new cancer vaccine to prevent cancer recurrence.

The technology combines infection-fighting T-cells with the vesicular
stomatitis virus that targets and destroys cancer cells while leaving
normal cells unharmed. The study, which has not yet been replicated in
humans, is significant because it describes a potential new therapy to
treat and prevent the spread of cancer in patients.

"We hope to translate these results into clinical trials. However,
until those trials are done, it's difficult to be certain that what we
see in mouse models will clearly translate to humans. We're hopeful
that will be the case," says Richard Vile, Ph.D., a Mayo Clinic
specialist in molecular medicine and immunology and the study's
principal investigator.

In primary cancers of the breast, colon, prostate, head and neck and
skin, the growth of secondary tumors often pose the most threat to
patients, not the primary tumor. The prognosis for these patients
often depends upon the degree of lymph node involvement and whether
the cancer has spread.

Dr. Vile and colleagues theorized that they could control the spread
of cancer through the lymphatic system (bone marrow, spleen, thymus
and lymph nodes) by manipulating the immune system.

Researchers zeroed in on immature T-cells from bone marrow,
programming them to respond to specific threats to the immune system
while delivering a cancer-destroying virus to the tumor cells.

To deliver the virus, researchers removed T-cells from a healthy
mouse, loaded them with the virus and injected the T-cells back into
the mouse. Researchers found that once the T-cells returned to the
lymph nodes and spleen, the virus detached itself from the T-cells,
found the tumor cells, selectively replicated within them and
extracted tumor cells from those areas.

Cancer Vaccine

The procedure used in this study triggered an immune response to
cancer cells, which means that it could be used as a cancer vaccine to
prevent recurrence.

"We show that if you kill tumor cells directly in the tumor itself,
you can get a weak immunity against the tumor, but if you use this
virus to kill tumor cells in the lymph nodes, you get a higher
immunity against the tumor," Dr. Vile says.

Results

The technique used in this study successfully treated the cells of
three different diseases: melanoma, lung cancer and colorectal cancer.
The results include:

Two days after treatment, the presence of melanoma tumor cells in
lymph nodes was significantly less, but not completely gone. There
were no cancer cells in the spleen.

Ten-to-14 days after a T-cell transfer, both the lymph nodes and
spleen were free of melanoma tumor cells.

Mice treated with a single dose of the T-cells transfer developed a
potent T-cell response against melanoma tumor cells.

Although the procedure was not intended to treat the primary melanoma
tumor, significant reductions in tumor cells were observed.

In mice with lung cancer metastasis, cancer cells were significantly
reduced in one-third of mice and completely eradicated in two-thirds
of mice. Efforts to clear metastases from colorectal tumors were
similarly effective.

Lung and colorectal tumor cells were purged from lymph nodes. Also,
the spleens of mice that had lung cancer developed immunity to the
cancer after the treatment.

The technology already exists to extract T-cells from patients, attach
the virus and inject the cells back into the patients. Doctors
currently use a similar process to attach radioactive tracers to T-
cells when trying to find the source of an infection in patients.

"This is technology that is relatively easy to translate to humans
because it involves taking T-cells from the patient -- something
routinely done today -- loading them with this virus and then putting
those T-cells back into patients whose cancer has spread to lymph
nodes, are at high risk of the cancer spreading to other parts of the
body or are at high risk of succumbing to the cancer," Dr. Vile says.

The study appeared in the Dec. 9 online issue of Nature Medicine.

Other authors of the study include: Jian Qiao, M.D., Ph.D.; Timothy
Kottke; Candice Willmon, Ph.D.; Feorillo Galivo; Phonphimon Wongthida;
Rosa Maria Diaz, Ph.D.; Jill Thompson and Pamela Ryno of the Molecular
Medicine Program at Mayo Clinic; Glen Barber of the Sylvester
Comprehensive Cancer Center, University of Miami School of Medicine;
John Chester, Peter Selby and Alan Melcher of the Cancer

Research UK Clinical Centre, Leeds Teaching Hospitals NHS Trust and
Leeds Institute of Molecular Medicine, University of Leeds, U.K.; and,
Kevin Harrington, The Institute of Cancer Research, London.

This study was funded by the National Institutes of Health and Mayo
Clinic.

Adapted from materials provided by Mayo Clinic.

http://www.sciencedaily.com/releases/2007/12/071218154220.htm