A new type of immunotherapy was highly effective against five types of childhood brain cancer when tested in mice. The treatment, which is already in clinical trials for other cancer forms in adults, looks promising as a method to improve the treatment of childhood brain cancer, for which current treatment is limited or even nonexistent.
A key aspect of the findings was that the treatment, in the form of an antibody, only targeted tumor cells, leaving other brain cells or developing cells unharmed. Researchers even believe that it may be safer than other types of immunotherapies.
The study, “Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors,” was published in the journal Science Translational Medicine.
To be, or not to be — eaten
The antibody seeks out and becomes attached to a protein called CD47 on the surface of the tumor cells. The factor is used as a flag to signal “don’t eat me” to immune cells that patrol the environment and engulf infected or abnormal cells.
While other cells do have this tag on their surface, they lack the corresponding “eat me” tag, reserved for abnormal cancer cells. To hide this molecule from the immune system, cancer cells produce large amounts of CD47, causing the “eat me” tag to get lost in a sea of molecules telling immune cells to look the other way.
When the antibodies bind to CD47, immune cells, called macrophages, suddenly see the tumor for what it is, and start engulfing the cells.
The mouse experiments, performed by researchers at Stanford University School of Medicine, proved that the treatment very efficiently shrank brain tumors.
The team tested the treatment on five different brain cancer types: Group 3 medulloblastoma; atypical teratoid rhabdoid tumor; primitive neuroectodermal tumor; pediatric glioblastoma; and diffuse intrinsic pontine glioma.
They grew the human cancer cells in lab dishes before they introduced them into the brains of mice. Images from the experiments spoke for themselves. While in untreated mice, the tumor — identified by a splash of colors in a black and white picture — lit up the entire head, while treated mice had only a few specks of color in their brain.
“The most exciting aspect of our findings is that no matter what kind of brain tumor we tested it against, this treatment worked really well in the animal models,” Samuel Cheshier, MD, PhD, and senior author of the study, said in a press release.
Safe approach for growing brains
When researchers injected normal human brain cells into mice brains, along with the tumors, the antibodies did not harm the normal cells. Also when mixing tumor cells and cells destined to become neurons, the antibodies allowed immune cells to kill only the tumors.
In fact, the team thinks that the antibodies may be even less toxic than other immunotherapies, which engage other types of immune cells.
Macrophages, which respond to the “eat-me” signal, engulf a cell and get rid of its contents in a safe way. In contrast, other immune cells may kill a cell without cleaning up afterward. Spilling the contents of dead cancer cells might alter an immune response to produce unwanted side effects, the researchers figure. This, however, is an idea that has not yet been tested.
A promise for future treatment
“For many of these tumors, there’s just no treatment,” said Cheshier, an assistant professor of neurosurgery and a pediatric neurosurgeon at Lucile Packard Children’s Hospital Stanford. “Diagnosis is synonymous with a death sentence.”
Also when treatments with chemo or radiotherapy are possible for these types of brain cancer, it is highly toxic to a developing brain, causing a range of devastating long-term consequences.
Nevertheless, the treatment was not perfect. While it significantly reduced the tumors, it did not entirely clear them. Researchers believe that this may be caused by difficulties for immune cells to penetrate large tumors.
But the team is open to the possibility to test the anti-CD47 antibodies in combination with other immunotherapies, or with lower doses of standard cancer treatments.
Researchers expect the treatment to reach human clinical trials in childhood cancers in one or two years.
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