An immunotherapy successfully and safely treated five different types of aggressive pediatric brain tumors in mice, according to a new study from researchers at Stanford University School of Medicine.
The antibody, called Hu5F9-G4, works against a cellular “don’t eat me” signal called CD47. The anti-CD47 antibody causes immune cells to surround and destroy tumors while keeping healthy brain cells intact.
Currently there are ongoing Phase 1 trials using anti-CD47 antibodies to treat advanced adult non-central nervous system solid cancers, but this is the first time they’ve been tested against pediatric brain tumors.
Human cancer cells were grown in a dish and implanted in mice to develop into five types of childhood brain tumors: Group 3 medulloblastoma, atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma and diffuse intrinsic pontine glioma.
“For many of these tumors, there’s just no treatment,” Samuel Cheshier, M.D., Ph.D., assistant professor of neurosurgery said in a prepared statement. “Diagnosis is synonymous with a death sentence.”
While radiation and chemotherapy offer options as existing therapies, they can be extremely toxic to a developing brain and result in severe physical and cognitive disabilities.
In the preclinical test, the team was able to demonstrate that the anti-CD47 antibodies narrowly target the cancer without damaging healthy brain cells.
“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,” Cheshier said. “There was no toxicity to normal human cells, but very, very active tumor-killing in vivo.”
The anti-CD47 thearpy gives macrophages, which are immune cells that find and destroy tumors, a hand in detecting cancer cell signals. Unlike healthy cells, cancer cells give out an “eat me” signal from their surface. However they mask this signal by producing large amounts of CD47 which sends a “don’t eat me” signal that is found on both cancerous and healthy cells. By blocking CD47, the antibody is able to reveal the “eat me” signal on the cancer cells again and macrophages are able to do their job destroying tumors while leaving healthy cells alone.
Importantly the antibody was able to cross the blood-brain barrier in mice, which some immunotherapies cannot. The antibodies significantly prolonged the lives of mice, with those receiving low and high doses of the treatment surviving 32 and 38 days respectively, compared to 21 days in the untreated control group.
Results also showed that after being treated with the anti-CD47 antibody, macrophages concentrated at the sties of tumors and were able to get inside.
It also stopped medulloblastomas from metastasizing to the spines of treated mice, which when occurring in children is 100 percent fatal.
The authors noted that while the antibody shrunk all five tumor types, it did not completely eliminate all tumors, so to maximize its effect the anti-CD47 treatment should likely be combined with other types of cancer treatment.
Cheshier and his team plan to investigate this further with patients potentially receiving lower doses of standard treatment along with combinations of immunotherapies.
“The question is: Can we wisely combine immune therapies and other approaches to make cancer treatment more efficacious and less toxic?” Cheshier stated.
Due to the positive results of the study and the ongoing adult trials using anti-CD27 antibodies, Cheshier expects that clinical trials in children with brain cancer will begin within one to two years.
The findings were published March 15 in Science Translational Medicine.