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Researchers prime immune system’s T cells with foreign antibodies to target cancer cell

Everyday our immune system defends us against bacterial and viral invaders. But there are some threats that this lifesaving system hasn't evolved to deal with. In the case of tumors, it can’t recognize the threat – the mutated cells still appear to the immune system as “us” and the out-of-control cancer flies under its radar. Or it perceives something beneficial as a threat, attacking healthy transplant organs because the markers on the cells’ surfaces are unfamiliar.

In a paper published today in Nature, Stanford researchers came up with an ingenious hack that used the body's organ rejection machinery to fight a wide variety of cancers. The work was done in mice, but preliminary investigations show the same mechanism working in human cancers.

Tthe most important thing is to see if we can bring this new approach into the clinic

The key lies in antibodies, the small chemicals that circulate through the body, attaching themselves to foreign proteins, including those on the surfaces of transplanted organs. These antibody protein combos are picked up by scavenging cells, called dendritic cells, and presented to T cells in a way that puts the T cells in attack mode, destroying any cells displaying these proteins.

As Edgar Engleman, MD, PhD, senior author on the paper, said, “T cells contain the bullet, but antibodies start the whole thing off."

We don’t make antibodies to the proteins on our own cells, or rather, antibodies that recognize “self” are purged early on. So there are no antibodies to recognize the mutated proteins of tumors. But, transplant those tumor cells into someone else, and in less than a week, the T cells begin to eliminate the cancer - at least that is what’s been observed in mice.

The researchers isolated antibodies from the mice that rejected the transplanted tumors. The antibodies, along with chemicals that stimulated the dendritic cells, were injected back into the original cancer-afflicted mice. In these mice, the immune system eliminated the tumors and the mice remained cancer free for a year.

The researchers found that the technique worked against six different mouse cancers. They also took cancers from four human patients, collected antibodies from donated blood plasma, and showed that, in a lab, human dendritic and T cells seemed to behave similarly to the mice cells. The researchers’ next step will be human trials.

"I honestly think the most important thing is to see if we can bring this new approach into the clinic," said Engleman. "That's where we want to go."

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: Oh, grow up! "Specialized" stem cells tolerated by immune system, say Stanford researchers, Training the immune system to attack cancer throughout the body a new clinical trial at Stanford and Video of killer T cells of immune system battling cancer

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