A Single Antibody to Treat Multiple Cancers?

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A single treatment to cure all cancers? Scientists may be one step closer.

In a recent study, scientists reported that they successfully tested an antibody treatment that shrank human breast, ovary, colon, bladder, brain, liver and prostate tumors transplanted into mice. The antibody blocks a protein called CD47, which normally sits on the cell surface and issues a “don’t eat me” signal that prevents the body’s immune system from attacking it.

Previous research has shown that CD47 resides on both tumor cells and healthy blood cells and keeps them safe from destruction by macrophages, a type of immune system cell. Cancerous cells use CD47 as a method to “hide” from the immune system’s fighters. About a decade ago, scientists at Stanford University School of Medicine, led by professor of pathology Irving Weissman, discovered that using an antibody to block CD47 cured some cases of leukemia and lymphoma in mice by allowing macrophages to seek and destroy the cancerous cells.

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In the new study, Weissman’s Stanford team showed that the CD47-blocking antibodies may also work against a number of other cancers. Analyzing cancer cells from patients with various tumors, the researchers found that CD47 existed on nearly every cell, which suggests that the protein may be common to all cancers. The researchers also found that cancer cells expressed about three times more CD47 than healthy cells.

The researchers started by exposing tumor cells to macrophages, and the CD47-blocking antibody treatment, in a petri dish. When the antibody wasn’t present, the tumor cells survived. But when the antibody bound itself to CD47 and blocked its “don’t eat me” signal, the macrophages destroyed the cancers.

The researchers then transplanted the various tumor cells into mice and allowed them to grow. When the animals were injected with the antibody, the tumors shrank, were less likely to spread, and even disappeared in come cases.

“If the tumor was highly aggressive, the antibody also blocked metastasis. It’s becoming very clear that, in order for a cancer to survive in the body, it has to find some way to evade the cells of the innate immune system,” said Weissman in a statement.

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The antibody treatment didn’t work in all cases. For instance, some mice injected with breast cancer cells from a human patient showed no changes after treatment. Yet in five mice with breast cancer, the antibody treatment cured them, with no signs of recurrence four months after treatment.

More research is needed on the relationship between macrophages and cancerous cells, the authors note. For example, reducing the size of a tumor with surgery or radiation before antibody treatment or using a second antibody to further stimulate immune system cells could boost success.

It’s also too early to say whether the antibody treatment would work on cancer cells in humans, where the tumors’ environment and behavior will be different from that in mice. To that end, Weissman’s team has received a $20 million grant from the California Institute for Regenerative Medicine to launch human safety tests, reports Science Now. “We have enough data already that I can say I’m confident that this will move to phase I human trials,” Weissman told Science Now.

The study was published [PDF] online Monday by the journal Proceedings of the National Academy of Sciences.

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