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Injection helps the immune system obliterate tumors, at least in mice

Tumors are growing on each side of this mouse’s body just behind its forelegs. 

Sagiv-Barfi et al./Science Translational Medicine

Our immune cells can destroy tumors, but sometimes they need a kick in the pants to do the job. A study in mice describes a new way to incite these attacks by injecting an immune-stimulating mixture directly into tumors. The shots trigger the animals’ immune system to eliminate not only the injected tumors, but also other tumors in their bodies.

“This is a very important study,” says immunologist Keith Knutson of the Mayo Clinic in Jacksonville, Florida, who wasn’t connected to the research. “It provides a good pretext for going into humans.”

To bring the wrath of the immune system down on tumors, researchers have tried shooting them up with a variety of molecules and viruses. So far, however, almost every candidate they’ve tested hasn’t worked in people.

Hoping to develop a more potent approach, medical oncologist Ron Levy of Stanford University in Palo Alto, California, and colleagues used mice to test the cancer-fighting capabilities of some 20 molecules, including several types of antibodies that activate immune cells. The researchers first induced tumors by inserting cancer cells just below the skin at two different locations on the animals’ abdomens. After tumors started growing at both sites, the scientists injected the molecules, alone or in combination, into one tumor in each mouse. They then tracked the responses of both tumors.

A pair of molecules—a type of DNA snippet called CpG and an antibody against the immune cell protein OX40—produced the best results. “On their own, they do almost nothing, but the combination is synergistic,” Levy says. When the researchers injected the two molecules into mouse tumors, they disappeared in less than 10 days. In less than 20 days, the noninjected tumors had also vanished, the team reports online today in Science Translational Medicine.

The two molecules rouse different immune cells. The DNA snippet stimulates dendritic cells, which help instigate counterattacks against tumors. OX40 functions as a throttle for T cells, another type of immune cell crucial for battling tumors, and the anti-OX40 antibodies rev up these cells.

Levy and his colleagues also tested the approach in a strain of mouse prone to breast tumors. If the animals harbored two tumors, injecting the mixture into one tumor curbed the growth of the second. Moreover, the combo prevented any new breast tumors from appearing.

“We think that this particular combination will be very effective in patients,” Levy says. He predicts that it could work against a variety of cancers. Because the combination destroys other tumors besides the injected one, it might eliminate metastases, or the secondary tumors that result when cancer spreads, he says.

“The data is very impressive, particularly for the uninjected tumors,” says cancer immunologist Drew Pardoll of the Bloomberg-Kimmel Institute for Cancer Immunotherapy in Baltimore, Maryland, who wasn’t connected to the study. The researchers “deserve a lot of credit” for testing the approach in the mice that spontaneously develop breast tumors, he says, which more closely mimic how cancer arises in humans.

The big question is whether the approach works in people, as most rodent cancer therapies don’t translate to humans. Levy and his colleagues are about to find out. They are launching a clinical trial to evaluate the safety of their approach and gauge its effectiveness in patients with lymphoma, a cancer of the lymphatic system.

News credit : Sciencemag

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