By Eryn Brown, Los Angeles Times –
LOS ANGELES — Blocking “don’t destroy me” signals that normally sit on the surface of tumor cells and render them resistant to immune-cell attack slows the growth of a broad range of human cancers when they’re implanted in mice, researchers have found.
The approach, reported by immunologists at the Stanford University School of Medicine, was effective against ovarian, breast, colon, bladder, liver, prostate and brain cancer cells. If the work can be repeated in people, the approach may someday help doctors marshal defender cells in patients’ own bodies to fight cancers, the researchers said.
Key to the work is a cell protein called CD47, which is already being investigated in the treatment of leukemia.
CD47 sits on cell membranes and communicates with various immune cells, including macrophages, which gobble up foreign invaders in the body. It plays an important role in the normal life cycle of healthy red blood cells, telling macrophages to leave the cells alone.
In the study, the scientists injected the animals with antibodies that bind to CD47 and block out its protective signal.
“If we can block this signal, we can get the immune system to eat (the cancer cells) up,” said Stephen Willingham, a postdoctoral researcher in the laboratory of immunologist Dr. Irving Weissman at Stanford and first author of a paper about the work.
The Stanford team examined cancer cells removed from patients with a variety of types of solid tumors. They found that CD47 studded the membranes of almost all of the cancer cells in their sample, suggesting that it is a molecule common to all cancers.
Placing the cells in lab dishes, the team administered an antibody: a protein that binds to CD47 and blocks it from warding off immune system cells. Macrophages ate the cells.
The researchers then implanted human tumor cells in mice for further study. They allowed the cancers to grow, and administered the antibody against CD47.
Antibody treatment inhibited the growth of almost all of the solid tumors and was able to wipe out some smaller cancers altogether, according to the report, which was published Monday in the journal Proceedings of the National Academy of Sciences.
Even when it didn’t destroy a large tumor, Willingham said, the antibody prevented the cancer from spreading and wiped out metastases scattered through the body.
The therapy worked better in some cases than in others. One breast cancer case didn’t respond to treatment at all.
“We never figured that out,” Willingham said.
Researchers who were not involved in the study called it an important incremental step toward a novel cancer therapy.
Paired with surgery or other treatments, it could be used to stimulate a patient’s immune system to fight cancer, said USC oncologist Dr. Heinz-Josef Lenz.
But scientists will have to evaluate the treatment’s effectiveness and safety in humans.
Although the mice in the Stanford experiment didn’t suffer severe side effects, that may not be the case in people. As with chemotherapy, “you run the risk of not only killing the tumor, but also the normal cells,” said David DiGiusto, a researcher at City of Hope in Duarte who was not involved in the study.
