Potential new therapy that kills cancer cells selectively

By Dr. Ananya Mandal, MDMar 28 2012

Researchers have made a drug that helps the immune system to break down cancerous tumors. It has worked on breast, bowel, prostate, ovarian, brain, bladder and liver cancers, while previous studies show it can also be used to fight some blood cancers. If given early, the drug could even be a cure, researchers say.

The antibody has so far been tested only on mice, but researchers hope to give it to people within two years.

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.

Tests on cells in the lab and on mice showed it to work on a broad range of cancers and with minimal side-effects. Given to mice with human tumors, the antibody made them shrink and, in some cases, disappear. The journal Proceedings of the National Academy of Sciences study adds that the drug ‘dramatically’ increased survival rates.

Researcher Dr Irving Weissman, from the Stanford University School of Medicine in California, said, “Blocking this “don’t-eat-me” signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity. This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy.”

“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 this work.

Dr Weissman said that when used on small tumors, the drug is ‘potentially curative’ – but stressed that for some of the mice it did not work at all. 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. He added that there was now enough evidence to ‘move forward quickly but cautiously’ into human trials. However, the need for extensive proof that the drug is safe as well as effective means that its widespread use is about a decade away.

Professor Philip Ashton-Rickardt, an expert in immunology funded by Cancer Research UK, said the research could lead to new treatments. “Particularly exciting is the possibility that this approach could be used to tackle cancer cells that are resistant to traditional treatments such as chemotherapy and radiotherapy,” he said. “But clinical trials are needed to find out whether it will benefit patients,” he said.

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.

Willingham said the only way to know how the antibody treatment will work in people will be to try it out. Plans to test the antibody therapy in leukemia patients in Britain are underway, funded by the California Institute of Regenerative Medicine. The team also hopes to test the treatment in patients with solid-tumor cancers within a couple of years, Willingham said.

Cancer researcher Tyler Jacks of the Massachusetts Institute of Technology in Cambridge says that although the new study is promising, more research is needed to see whether the results hold true in humans. “The microenvironment of a real tumor is quite a bit more complicated than the microenvironment of a transplanted tumor,” he notes, “and it's possible that a real tumor has additional immune suppressing effects.” Another important question, Jacks says, is how CD47 antibodies would complement existing treatments. “In what ways might they work together and in what ways might they be antagonistic?” Using anti-CD47 in addition to chemotherapy, for example, could be counterproductive if the stress from chemotherapy causes normal cells to produce more CD47 than usual.