Antibody shows promise in 5 kinds of childhood brain cancer

Li Ka Shing Center for Learning and Knowledge
While some treatments can be effective in pediatric brain tumors, they often have toxic effects on the brain. The antibody Hu59-G4 shrank five types of tumors without harming surrounding tissue in mouse models.

Stanford researchers have found that a recently developed antibody reduced the size of five different types of tumors in mouse models of childhood brain cancer. The treatment, dubbed Hu5F9-G4, also specifically targeted malignant cells, sparing healthy tissue.

Tumors shrank and survival improved in mouse models of medulloblastomas, atypical teratoid rhabdoid tumors, primitive neuroectodermal tumors, pediatric glioblastomas and diffuse intrinsic pontine gliomas. The treatment also stopped medulloblastoma—the most aggressive form of pediatric cancer—from spreading to the mice’s spines.

The team’s work centered on the protein CD47, which is present on many cells in the body and helps differentiate healthy cells from aging or diseased cells that should be destroyed by immune cells. Cells that express this protein send a signal to macrophages not to engulf and digest them. But “nearly every kind” of cancer cell has CD47 too, according to Stanford University.

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Last year, Stanford spun out a new company, dubbed Forty Seven, to develop the antibody, Hu5F9-G4. The startup secured a $75 million commitment from the likes of Sutter Hill Ventures and Alphabet’s venture capital investment arm, GV. The antibody is in two Phase 1 trials for patients with solid tumors and for patients with acute myeloid leukemia.

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Hu5F9-G4 blocked CD47 by “unmasking” the tumor cells to macrophages, the researchers said. The antibody didn’t harm healthy brain tissue surrounding the tumors, and it spared noncancerous nerve cells in culture. It showed promise as a new treatment, either alone or as a combination therapy, the researchers said.

Another Stanford team is investigating a combination approach to fight medulloblastoma. They found the chemo drug vismodegib is effective against medulloblastoma, but only until it mutates and develops resistance. By pairing vismodegib with an approved COPD drug, the team managed to target a different signaling pathway and sidestep the tumor's drug resistance.

The new research on Hu5F9-G4 in childhood brain cancers was published in the journal Science Translational Medicine. In their discussion of the results, the authors note that new treatments for childhood brain tumors are in high demand, because even when children beat their cancers, complications from the treatments can produce serious cognitive defects. They also suggest that combining anti-CD47 antibodies with tumor-specific treatments may prove to be the most effective way to eliminate brain tumors.

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