May 29, 2003 

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Cancer-proof Mice (video)
May 06, 2003

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Interviewee: Zheng Cui, Wake Forest University Baptist Medical Center.

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Produced by Joyce Gramza

Copyright © ScienCentral, Inc., with additional footage from Wake Forest University.

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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.

by Karen Lurie

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