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Wednesday, 28 March 2012

A single drug can shrink or cure human breast, ovary, colon, bladder, brain, liver and prostate tumours in mice -

A single drug can shrink or cure human breast, ovary, colon, bladder, brain, liver and prostate tumours in mice - 

A single drug can shrink or cure human breast, ovary, colon, bladder, brain, liver and prostate tumours that have been transplanted into mice, researchers have found. The treatment, an antibody that blocks a “do not eat” signal normally displayed on tumour cells, coaxes the immune system to destroy the cancer cells.

A decade ago, biologist Irving Weissman, of the Stanford University School of Medicine in Palo Alto, Calif., discovered that leukemia cells produce higher levels of a protein called CD47 than do healthy cells. CD47, he and other scientists found, is also displayed on healthy blood cells; it’s a marker that blocks the immune system from destroying the cells as they circulate. Cancers take advantage of this flag to trick the immune system into ignoring them. In the past few years, Weissman’s lab showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize the cancer cells as invaders. Now, he and colleagues have shown that the CD47-blocking antibody may have a far wider impact than just blood cancers.

“What we’ve shown is that CD47 isn’t just important on leukemias and lymphomas,” says Weissman. “It’s on every single human primary tumour that we tested.” Moreover, Weissman’s lab found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumour made could predict the survival odds of a patient.

To determine whether blocking CD47 was beneficial, the scientists exposed tumour 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 CD47 was present, the macrophages engulfed and destroyed cancer cells from all tumour types.

Next, the team transplanted human tumours into the feet of mice, where tumours can be easily monitored. When they treated the rodents with anti-CD47, the tumours shrank and did not spread to the rest of the body. In mice given human bladder cancer tumours, for example, 10 of 10 untreated mice had cancer that spread to their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. Moreover, the implanted tumour often got smaller after treatment — colon cancers transplanted into the mice shrank to less than one-third of their original size, on average. And in five mice with breast cancer tumours, anti-CD47 eliminated all signs of the cancer cells, and the animals remained cancer-free four months after the treatment stopped.

“We showed that even after the tumour has taken hold, the antibody can either cure the tumour or slow its growth and prevent metastasis,” says Weissman.

Although macrophages also attacked blood cells expressing CD47 when mice were given the antibody, the researchers found that the decrease in blood cells was short-lived; the animals turned up production of new blood cells to replace those they lost from the treatment, the team reported online Monday in the Proceedings of the National Academy of Sciences.

Cancer researcher Tyler Jacks, of the Massachusetts Institute of Technology, says that although the new study is promising, more research is needed to see whether the results hold true in humans.

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