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The
Mouse in Science - Cancer Research
American
Cancer Society
A patient has end-stage cancer and suddenly, inexplicably, his cancer disappears.
At last, scientists have proof of how that can happen.
As this ScienCentral News video reports, they’ve accidentally discovered
a cancer-proof mouse.
Mighty Mouse
We have all heard stories of cancer patients who've experienced miraculous
cures. We call it a miracle, but cancer researchers call it “spontaneous
regression.” These cases are rare, and almost impossible to follow up
on. But researchers at Wake Forest University now have a colony of mice whose
immune systems destroy cancer cells.
As they write in the May 27, 2003 issue of Proceedings
of the National Academy of Sciences, a team led by Zheng
Cui, associate professor of pathology at the Wake
Forest University Baptist Medical Center, discovered a mouse that just
wouldn’t get cancer, despite being injected repeatedly with aggressive
cancer cells.
“This mouse can withstand the challenge of an almost unlimited number
of cancer cells,” says Cui. “We tried 500,000, we tried 5 million,
we tried 50 million, we tried 500 million. We even tried several billion cancer
cells injected into this mouse. Surprisingly to all of us here, none of these
injections caused this mouse to develop cancer. But all the other normal mice
will develop cancer even with a very small number of cancer cells injected.”
Also amazing, says Cui, is that normal cells are unharmed—the mice stay perfectly
healthy. “If you consider the current therapy in humans, we have to
endure very profound side effects to kill cancer cells,” says Cui. “However,
in these mice, what was amazing to us is that they don't seem to have a side
effect. They can selectively kill cancer cells.”
Cui believes the mouse must have had a mutation in a single gene. It transmitted
the trait to half its offspring, displaying "a perfect Mendelian
single dominant gene pattern,” says Cui. The scientists have since
bred a colony of some 700 of the mice and are working to identify the gene
and the mutation. "If we can find out…how this mutation can function
to activate immune cells, to allow immune cells to recognize these cancer
cells and be able to destroy them," he says, "hopefully we can learn
from this mouse study and then design similar strategies in human therapies.”
They do have some clues. The immune system cells that recognize and kill the
cancer cells are part of the innate
immune system. The researchers also found that if they collected these
immune cells from a cancer-resistant mouse and injected it into normal mice
"that were otherwise very sensitive to the cancer cells, then these normal
mice would acquire similar ability to eradicate these cancer cells,"
says Cui.
The cancer resistance is also age-dependent. The younger the mice are when
they’re exposed to the cancer, the more quickly their immune systems
react to kill the cancer cells. Once they have resisted cancer, they are protected
for life. “However, when you inject the mouse very late with cancer
cells, let's say at one year of age, their offspring can be cancer resistant,
but these parents will not, because somehow old age will prevent the expression
of these resistant mechanisms,” Cui says. Because cancer is generally
a disease of aging, this suggests that there may be a way to "vaccinate"
the immune system against cancer.
New Therapies
The discovery of the cancer-resistant mouse doesn't mean any change in cancer
treatments for humans yet. “This is a study just in mice now, although
we are quite excited," Cui says. "We hope that we can work hard
enough and be smart enough to figure out this mechanism in the shortest possible
time."
Cui says possible strategies for human patients might include "using drugs
to stimulate similar pathways, or to use gene therapy to simply put the mutated
gene or similar genes with similar mutations into the white blood cells or
even into bone marrow stem cells that will allow similar cancer-killer cells
to be created.”
He hopes the research will reveal how our own immune systems can be mobilized
against disease. “I think we can learn a lot through this model about
cancer cells and about ourselves. That is, our own bodies have great potential
to be used for therapies against disease."
The funders of this research were Wake
Forest University, the Charlotte
Geyer Foundation, the National
Cancer Institute, and the Cancer
Research Institute.