a single drug can shrink or cure tumors of the breast, ovary, colon, bladder, brain, liver and of the human prostate that were transplanted into mice, researchers have found. The treatment, an antibody that blocks a "do not eat" signal normally displayed on tumor cells, coaxes the immune system to destroy cancer cells.
There are ten, biologist Irving Weissman of school of medicine Stanford University in Palo Alto, California, discovered that leukemia cells produce higher levels of a protein called CD47 than healthy cells. CD47, he and other scientists found, is also displayed on healthy blood cells.. it is a marker that blocks the immune system to destroy them as they circulate Cancers take advantage of this flag to trick the immune system into ignoring the past years, the lab Weissman showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize cancer cells as invaders. Now he and his colleagues have shown that the CD47-blocking antibody may have a much larger impact than just blood cancers.
"What we have shown that CD47 is not just important on leukemias and lymphomas," says Weissman. "He's on every single human primary tumor that we tested." In addition, the laboratory Weissman found that cancer cells have always had higher levels of CD47 than did the healthy cells. How much CD47 a tumor made could predict the chances of survival of a patient.
To determine whether blocking CD47 was beneficial, the scientists exposed tumor cells to macrophages, a type of immune cell, and anti-CD47 molecules in petri dishes. Without the drug, the macrophages ignored the cancerous cells. But when the anti-CD47 antibody was present, sunken macrophages and destroys cancer cells of all types of tumors.
The team then transplanted in mouse feet, where the tumor can be easily monitored human tumors. When they treated the rodents with anti-CD47, the tumors shrank and did not spread to the rest of the body. In mice, since tumor cancer of the human bladder, for example, 10 untreated 10 mice had cancer which propagate in their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. In addition, the implanted tumor often got smaller after colon cancer treatment-transplanted into mice decreased to less than a third of their original size, on average. After five mice with breast cancer tumors, anti-CD47 eliminated all signs of cancer cells, and the animals remained 4 months after stopping treatment without cancer.
"We have shown that even after the tumor has taken hold, the antibody can either cure the tumor or slow its growth and prevent metastasis," said Weissman.
Although as macrophages also attacked blood cells expressing CD47 when mice received the antibody, the researchers found that the reduction in blood cells was short-lived; the animals turned into production of new blood cells to replace those that they lost the treatment, the team announced today online in the Proceedings of the national Academy of sciences .
Tyler Jacks cancer researcher at the Massachusetts Institute of Technology in Cambridge says that while the new study is promising, more research is needed to see if the results hold in humans. "the microenvironment of a real tumor is a bit more complicated than the microenvironment of a transplanted tumor, "he notes," and it is possible that a real tumor has additional immune suppression effects. "
another important issue, Jacks said, is how the CD47 antibody complement existing treatments. "How can they work together and how they might be antagonistic?" Using anti-CD47 antibody in addition to chemotherapy, for example, could be cons-productive if the stress of chemotherapy causes normal cells CD47 to produce more than usual.
Weissman's team received a grant of $ 20 million from the California Institute for Regenerative Medicine to move the results of mouse studies to human safety tests. " We have enough data already, "says Weissman," I can say that I am convinced that it will move to phase I human trials. "
* Fixed April 2, 2013: A reference to the compound used to treat mice has been named as CD47, but in all cases was the antibody to this protein, anti-CD47.
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