Antibody fights pediatric brain tumors in preclinical testing | News … – Stanford Medical Center Report

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, said Cheshier, who is also a pediatric neurosurgeon at Lucile Packard Childrens Hospital Stanford. In mice that had been implanted with both normal human brain cells and human brain cancer cells, there was no toxicity to normal human cells but very, very active tumor-killing in vivo, he said.

Given the encouraging results of the new study and the ongoing research on anti-CD47 antibodies in adults, the antibodies are expected to reach clinical trials in children with brain cancer in one to two years, he added.

The anti-CD47 antibodies help the immune system to detect an important difference between cancerous and healthy cells: Cancer cells make eat me signals that are displayed on their cell surfaces, while healthy cells do not. However, cancer cells hide these eat me signals by producing large quantities of CD47, a dont eat me protein that is found on the surface of both healthy and malignant cells. When CD47 is blocked by antibodies, immune cells called macrophages can detect the cancer cells eat me signals. Macrophages then selectively target, engulf and destroy the cancer cells without harming healthy cells, because normal cells lack the eat me signals.

The Stanford team conducted a long series of experiments using different combinations of tumor cells and healthy cells in culture, as well as in various mouse models in which human brain cancer cells had been implanted in mice. Highlights of their experiments included the following:

The anti-CD47 antibodies did not completely eliminate all tumors, suggesting that the antibodies may not be able to completely penetrate large tumors, the researchers noted.

To maximize their effects, the antibodies will likely need to be combined with other forms of cancer treatment, a concept the researchers plan to investigate further, Cheshier said. In the future, patients may receive combinations of immune therapies and lower doses of standard cancer treatments, he said, adding, The question is: Can we wisely combine immune therapies and other approaches to make cancer treatment more efficacious and less toxic?

Anti-CD47 antibodies also may have an advantage over other immunotherapies in that they activate macrophages, which completely engulf and eat cancer cells, Cheshier noted. In many forms of immunotherapy, the cells you target die and spill their contents, which can cause dysregulated immune responses, he said. Anti-CD47 antibodies may produce fewer such side effects, though the idea remains to be tested.

Other Stanford co-authors of the paper are medical students Abdullah Feroze, Rogelio Esparza and Michael Zhang; postdoctoral scholars Suzana Kahn, PhD, Anne Volkmer, MD and Stephen Willingham, PhD; research assistants Anitha Ponnuswami, Theresa Storm, Cyndhavi Narayanan and Pauline Chu; senior research associate Jie Liu, MD, PhD; undergraduate research associate Chase Richard; Aaron McCarthy, a former life sciences research professional and animal colony manager; Patricia Lovelace, research and development engineer; Simone Schubert, life science researcher; visiting scholar Gregor Hutter, MD, PhD; Griffith Harsh, MD, professor of neurosurgery; Michelle Monje, MD, PhD, assistant professor of neurology; Yoon-Jae Cho, MD, a former assistant professor of neurology and neurological sciences; Ravi Majeti, MD, PhD, associate professor of medicine; senior scientist Jens Volkmer, MD; Paul Fisher, MD, professor of pediatrics; Gerald Grant, MD, associate professor of neurosurgery; Gary Steinberg, MD, PhD, professor of neurosurgery; Hannes Vogel, MD, professor of pathology and of pediatrics; and Michael Edwards, MD, professor of neurosurgery.

Cheshier, Monje, Majeti, Fisher, Grant and Edwards are members of Stanfords Child Health Research Institute. Cheshier, Weissman, Harsh, Monje, Majeti, Fisher, Grant, Vogel and Edwards are members of the Stanford Cancer Institute. Weissman is the director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and of the Ludwig Center for Cancer Stem Cell Research and Medicineat Stanford.

Scientists from SickKids, the Hospital for Sick Children in Toronto; University Hospital, Dusseldorf; and Johns Hopkins University also contributed to the study.

The study was funded by National Institute of Neurological Disorders and Stroke (grant NINDSK08NS070926); the National Cancer Institute (grant P30CA006973); the California Institute for Regenerative Medicine; the Price Family Charitable Fund; the Center for Childrens Brain Tumors at Stanford; St. Baldricks Foundation; the American Brain Tumor Foundation; the Seibel Stem Cell Institute; the Pew Charitable Trusts; the Dr. Mildred-Scheel Foundation/German Cancer Aid; the German Research Foundation; the McKenna Claire Foundation; the Matthew Larson Foundation; Alexs Lemonade Stand Foundation; The Cure Starts Now; the Lyla Nsouli Foundation; the Dylan Jewett, Connor Johnson, Zoey Ganesh, Dylan Frick, Abigail Jensen, Wayland Villars and Jennifer Kranz memorial funds; the Virginia and D. K. Ludwig Fund for Cancer Research; the Lucile Packard Foundation for Childrens Health; the National Institutes of Health (grant UL1TR001085); the Tashia and John Morgridge Endowed Pediatric Faculty Scholar and Fellowships Awards; and the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases. The study was also funded by gifts from George Landegger; Rider and Victoria McDowell; Charles Comey and Judith Huang; and Colin and Jenna Fisher.

Stanfords Department of Neurology & Neurological Sciences also supported the work.

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Antibody fights pediatric brain tumors in preclinical testing | News ... - Stanford Medical Center Report