Cancer Curing Blood
SciCentral News ^ | June 7, 2006 | by Eva Gladek and Joyce Gramza
It's a discovery in animals that would change everything if it turns out to be true in people. An injection of blood cells from cancer-resistant mice cures cancer in ordinary mice. As this ScienCentral News video explains, there may be a way to identify cancer-resistant people.
The End of Cancer?
A universal treatment that would work against any type of cancer has always seemed like a far-fetched fantasy. But now researchers at Wake Forest University have made a discovery in mice that might one day lead to a "magic bullet" against human cancers if it proves to be true in people. Several years ago, the researchers identified a rare strain of mouse immune to high, usually lethal doses of cancer cells. Now they have shown that not only are these mice cancer-resistant, but their immune cells are also capable of curing normal, non-resistant mice of any type of advanced cancer.
As reported in Proceedings of the National Academy of Sciences, lead researcher Zheng Cui and his team injected white blood cells from the cancer-resistant mice into normal mice with aggressive cancers that should have killed them in two to three weeks. Instead, their cancer disappeared.
"Cancer cells had already developed a large tumor in the mice, and at a different place [than] where we put the immune cells in," says Cui, "That would require the immune cells to find them at a different part of the body and then track them down to the site and destroy the cancer cells."
The researchers have bred a large colony of the cancer-resistant mice, all from one mouse they discovered in 1999.
In previous studies the team showed that the resistant mice can survive very large doses ? up to 3 billion cells ? of any kind of cancer. This resistance is passed on genetically in a "perfect Medelian single dominant gene pattern," says Cui, since the trait is transmitted to roughly half of each resistant-mouse's offspring. On this basis the scientists believe the resistance mutation must be in a single gene.
But after seven years of searching for the gene, the researchers have yet to identify it. "There isn't any reason to think it's not a single gene, it just turns out that analysis of that genetics is somewhat more complex than one would have predicted," says pathologist Mark Willingham, a co-author of the paper.
Their past work also clearly showed that the gene worked by somehow activating the immune systems of these resistant mice to selectively target cancer cells. Their most recent research confirms that the immune cells that do the cancer killing belong to the innate immune system. They recognize cancer cells as foreign and attack them without having any prior exposure to them.
"I think the surprise from this mouse model is that it involves a part of the immune system that would not have been predicted," says Willingham.
When the researchers isolated different types of innate immune system cells from the resistant mice and tested them against cancer cells, they got another surprise: the cancer resistance was not confined to just one type of immune cell. "All [the types] can be independently killing [cancer] cells without the other subtypes present," says Cui.
A funder of the study, the Cancer Research Institute, which backs immunological approaches to cancer diagnosis and treatment, is funding collaborations with Bruce Beutler, M.D., an immunogeneticist at the Scripps Research Institute, to help search for the gene, and with Robert D. Schreiber, Ph.D., a molecular immunopathologist at the Washington University School of Medicine in St. Louis, who will test the cancer-resistant cells on his mouse models of naturally arising cancers.
Unconventional ideas
The researchers also developed a blood test that can identify the cancer-resistant mice without having to challenge them with cancer. They hope a similar test might help find and study cancer-resistance in people.
"If this were to be the same in humans we could simply identify cancer-resistant humans and to do the blood transfusion or white blood cell transfusion without even knowing the mechanism to find out whether it will work or not," says Cui, "So that's obviously on everybody's mind."
The researchers say they've heard from many cancer patients and their loved ones excited about the tantalizing possibility that blood and bone marrow banks might also contain cancer curing cells. Cui points out that it could take years to find the gene, and many more to develop and test drugs that target it. In the meantime, his team has begun to test blood samples from healthy people, and have found a wide range of cancer-killing activity in humans. "We are forced and compelled to do this kind of experiment ... I think it's our responsibility as cancer researchers," Cui says. But he also acknowledges that he is having a hard time getting funding for this approach. "It's obviously a very unconventional way of doing science nowadays," he says. "It's not mechanism-based ... it?s simple mimicry of what happened in the mice."
Indeed, cell biologist Jill O'Donnell-Tormey, executive director of the Cancer Research Institute, says it's important to first understand the genetic and biological basis of these cancer killing blood cells.
"There is some indication that a similar mechanism that we're seeing in these remarkable mice are also present in humans but we think we have a ways to go in terms of doing a good deal of research before we can actually answer that question," she says.
Cui says he would like to pursue both the conventional and unconventional approaches. "We think there might actually be a possibility we could do it without knowing the mechanism," he says, "but of course by knowing the mechanism you could devise many other options, so if one thing doesn't work then you can also find different ways using the same concept. So we think both directions are important."
He notes, however, that if the cell-donation approach were to work in people, it would not need to go through a long FDA approval process. "All the delivery mechanisms are already in place and all the ethical regulations for that direction are already in place. So if we can identify cancer-resistant humans then they could start treating them tomorrow if someone wants to pay for it."
This most recent finding by Cui and his team was published in the May 16, 2006 Proceedings of the National Academy of Sciences (PNAS). The research is funded by the Cancer Research Institute (CRI), National Cancer Institute (NCI), and the Charlotte Geyer Foundation.
SciCentral News ^ | June 7, 2006 | by Eva Gladek and Joyce Gramza
It's a discovery in animals that would change everything if it turns out to be true in people. An injection of blood cells from cancer-resistant mice cures cancer in ordinary mice. As this ScienCentral News video explains, there may be a way to identify cancer-resistant people.
The End of Cancer?
A universal treatment that would work against any type of cancer has always seemed like a far-fetched fantasy. But now researchers at Wake Forest University have made a discovery in mice that might one day lead to a "magic bullet" against human cancers if it proves to be true in people. Several years ago, the researchers identified a rare strain of mouse immune to high, usually lethal doses of cancer cells. Now they have shown that not only are these mice cancer-resistant, but their immune cells are also capable of curing normal, non-resistant mice of any type of advanced cancer.
As reported in Proceedings of the National Academy of Sciences, lead researcher Zheng Cui and his team injected white blood cells from the cancer-resistant mice into normal mice with aggressive cancers that should have killed them in two to three weeks. Instead, their cancer disappeared.
"Cancer cells had already developed a large tumor in the mice, and at a different place [than] where we put the immune cells in," says Cui, "That would require the immune cells to find them at a different part of the body and then track them down to the site and destroy the cancer cells."
The researchers have bred a large colony of the cancer-resistant mice, all from one mouse they discovered in 1999.
In previous studies the team showed that the resistant mice can survive very large doses ? up to 3 billion cells ? of any kind of cancer. This resistance is passed on genetically in a "perfect Medelian single dominant gene pattern," says Cui, since the trait is transmitted to roughly half of each resistant-mouse's offspring. On this basis the scientists believe the resistance mutation must be in a single gene.
But after seven years of searching for the gene, the researchers have yet to identify it. "There isn't any reason to think it's not a single gene, it just turns out that analysis of that genetics is somewhat more complex than one would have predicted," says pathologist Mark Willingham, a co-author of the paper.
Their past work also clearly showed that the gene worked by somehow activating the immune systems of these resistant mice to selectively target cancer cells. Their most recent research confirms that the immune cells that do the cancer killing belong to the innate immune system. They recognize cancer cells as foreign and attack them without having any prior exposure to them.
"I think the surprise from this mouse model is that it involves a part of the immune system that would not have been predicted," says Willingham.
When the researchers isolated different types of innate immune system cells from the resistant mice and tested them against cancer cells, they got another surprise: the cancer resistance was not confined to just one type of immune cell. "All [the types] can be independently killing [cancer] cells without the other subtypes present," says Cui.
A funder of the study, the Cancer Research Institute, which backs immunological approaches to cancer diagnosis and treatment, is funding collaborations with Bruce Beutler, M.D., an immunogeneticist at the Scripps Research Institute, to help search for the gene, and with Robert D. Schreiber, Ph.D., a molecular immunopathologist at the Washington University School of Medicine in St. Louis, who will test the cancer-resistant cells on his mouse models of naturally arising cancers.
Unconventional ideas
The researchers also developed a blood test that can identify the cancer-resistant mice without having to challenge them with cancer. They hope a similar test might help find and study cancer-resistance in people.
"If this were to be the same in humans we could simply identify cancer-resistant humans and to do the blood transfusion or white blood cell transfusion without even knowing the mechanism to find out whether it will work or not," says Cui, "So that's obviously on everybody's mind."
The researchers say they've heard from many cancer patients and their loved ones excited about the tantalizing possibility that blood and bone marrow banks might also contain cancer curing cells. Cui points out that it could take years to find the gene, and many more to develop and test drugs that target it. In the meantime, his team has begun to test blood samples from healthy people, and have found a wide range of cancer-killing activity in humans. "We are forced and compelled to do this kind of experiment ... I think it's our responsibility as cancer researchers," Cui says. But he also acknowledges that he is having a hard time getting funding for this approach. "It's obviously a very unconventional way of doing science nowadays," he says. "It's not mechanism-based ... it?s simple mimicry of what happened in the mice."
Indeed, cell biologist Jill O'Donnell-Tormey, executive director of the Cancer Research Institute, says it's important to first understand the genetic and biological basis of these cancer killing blood cells.
"There is some indication that a similar mechanism that we're seeing in these remarkable mice are also present in humans but we think we have a ways to go in terms of doing a good deal of research before we can actually answer that question," she says.
Cui says he would like to pursue both the conventional and unconventional approaches. "We think there might actually be a possibility we could do it without knowing the mechanism," he says, "but of course by knowing the mechanism you could devise many other options, so if one thing doesn't work then you can also find different ways using the same concept. So we think both directions are important."
He notes, however, that if the cell-donation approach were to work in people, it would not need to go through a long FDA approval process. "All the delivery mechanisms are already in place and all the ethical regulations for that direction are already in place. So if we can identify cancer-resistant humans then they could start treating them tomorrow if someone wants to pay for it."
This most recent finding by Cui and his team was published in the May 16, 2006 Proceedings of the National Academy of Sciences (PNAS). The research is funded by the Cancer Research Institute (CRI), National Cancer Institute (NCI), and the Charlotte Geyer Foundation.
hopefully it works out!
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