Anti-CD47 antibody shows promise against childhood brain tumors
A study led by researchers from the USA, Canada, Germany, and Switzerland now has shown that a humanized antibody that blocks the CD47 protein on tumor cells shows promise against a variety of pediatric brain tumors. The findings, reported 15 Mar 2017 in Science Translational Medicine, provide a therapeutic strategy for these hard-to-treat diseases.
CD47 is a membrane protein that is involved in many cellular processes, such as proliferation, apoptosis, adhesion, and migration. Previous research has determined that CD47 is overexpressed in all cancer cells, making it an attractive target for drug design. In cancer, CD47 acts as a "don't eat me" signal -- it prevents the innate immune system macrophages from engulfing and killing the cancer cells. Blocking this "don't eat me" signal with therapeutics such as an antibody has been considered a potential way to combat diverse cancers.
Currently, anti-CD47 antibodies are already being tested in clinical trials in adults who have tumors outside the central nervous system. In the new study, researchers including Dr Samuel Cheshier from the Stanford University School of Medicine conducted experiments to evaluate the effectiveness of these antibodies on patient-derived xenograft models of five aggressive and etiologically distinct pediatric brain tumors.
Although dramatic improvements in survival have been achieved, the mortality of childhood malignant primary brain tumors is still high. For most childhood brain tumors, the cause remains unknown and the optimal treatment regimen has not been determined. Some patients receive toxic radiotherapy and chemotherapy that engender serious side effects. The antibodies tested in this study hold a big advantage over the traditional therapies: they effectively kill tumor cells without affecting normal cells.
The researchers found that all the five types of brain tumors expressed the CD47 "don't eat me" signal and an "eat me" signal known as CRT. In vitro experiments showed that treatment with a humanized anti-CD47 antibody called Hu5F9-G4 caused the cancer cells to be engulfed and killed by macrophages while sparing normal brain cells.
Hu5F9-G4 also demonstrated therapeutic efficacy in vivo in mice implanted with pediatric brain tumors. The antibody was able to cross the blood-brain barrier. Mice treated with the antibody had prolonged survival. By examining the animals' brain, the researchers found that macrophages got inside the tumors and that the antibody treatment did not completely eliminate all tumors. This leads to a concept that combining the antibody with another cancer therapy may optimize the therapeutic effect.
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