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Ludwig Stanford researchers show "don't eat me" antibody could help treat pediatric brain tumors

Ludwig Institute for Cancer Research News Apr 14, 2017

Five types of pediatric brain cancer were safely and effectively treated in mice by an antibody that causes immune cells to engulf and eat tumors without hurting healthy brain cells, according to a new study led by Ludwig Stanford Director Irving Weissman and Samuel Cheshier, an investigator at the Ludwig Center at Stanford and an assistant professor of neurosurgery at the Stanford University School of Medicine.

The antibody stops transmission of “don’t eat me” signals from a cell surface protein called CD47. With the antibody in place, “eat me” proteins that are unique to cancer cells are revealed, allowing immune cells called macrophages to engulf and destroy the tumor cells. It is already being tested as a cancer therapy in early clinical trials. This is, however, the first indication that it might work as a treatment for pediatric brain tumors.

The study was published in the journal Science Translational Medicine.

Many childhood brain tumors are inoperable, while others cannot be treated by existing chemotherapies. Others require radiation and chemotherapy so toxic to the developing brain that treatment can cause devastating long–term side effects. The anti–CD47 antibodies, in contrast, allow the immune system to specifically target cancer cells while leaving healthy brain cells alone. Weissman and his colleagues tested the efficacy of anti–CD47 antibodies against five aggressive types of pediatric brain tumors: Group 3 medulloblastoma, atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma and diffuse intrinsic pontine glioma. However, the anti–CD47 antibodies did not completely eliminate tumors, perhaps because they did not reach all parts of relatively large ones, the researchers noted. The researchers suspect the antibodies will need to be combined with other forms of cancer treatment, a concept they plan to investigate further.

The low toxicity is a big contrast to existing therapies for pediatric brain tumors, which can be very harmful to children’s developing brains.

The antibodies don’t appear able to completely rid the body of large tumors on their own, the researchers caution. However, they hope that combining this form of immunotherapy with low doses of other cancer treatments may provide a treatment that is both more effective and less damaging than existing options.

Because the anti–CD47 antibodies are already being tested in a phase–1 clinical trial of adults with other forms of cancer, the researchers anticipate that the therapy will be tried in children with brain cancer fairly soon, probably within the next year or two.
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