“A new antibody therapy could dramatically improve outcomes for pediatric tumors.”
What This Project Does
A research team at Stanford University led by Drs. Kathleen Sakamoto and Irv Weissman has received a $1.37 million grant from CureSearch titled “Development of CD47 Monoclonal Antibody Therapy for Pediatric Tumors.” Drs. Sakamoto and Weissman are developing a Phase I study using a new antibody treatment. Phase I clinical trials are the earliest stage of testing a new treatment. In a Phase I trial, researchers test a new treatment on a small group of patients to find out if a drug is safe, what its side effects are, and most importantly, whether it works to treat cancer.
In a healthy person, when the body makes abnormal cells or cells become old, the body’s scavenger cells, called macrophages, eliminate them in a process defined as programmed cell removal. When a person has cancer, the abnormal cells are not eliminated by the macrophages. Researchers under the leadership of Dr. Irv Weissman discovered that pediatric brain tumor, leukemia, bone tumor and neuroblastoma cells overproduce a cell surface protein known as CD47. The overproduction of CD47 on cancer cells tells macrophages “don’t eat me,” allowing the disease to progress. The members of Dr. Weissman’s team (Drs. Sam Cheshier, Jens Peter-Volkmer, and Sid Mitra) have successfully tested an antibody to block the “don’t eat me signal” in a variety of cancer cells and in animals. The CureSearch grant will support this research team in conducting a Phase I clinical trial at the Lucile Packard Children’s Hospital at Stanford University. Their study will test whether anti-CD47 monoclonal antibody will decrease the size of tumors in children, by blocking the CD47 “don’t eat me” signal and allowing macrophages to eliminate cancer cells.
Potential Impact on Children
There many types of childhood tumors, but brain tumors are the most common solid tumor in children. The clinical trial developed by Dr. Sakamato and Dr. Weissman will treat children with brain tumors using their novel antibody therapy. In early studies, Dr. Weissman has shown that the antibody treatment is more effective and better tolerated than standard chemotherapy. Because antibody therapy uses the body’s own immune system to kill cancer cells, it is easier to tolerate and has fewer side effects than toxic chemotherapies. If the trial is successful, this therapy could be widely used to treat childhood tumors.
18 Month Research Update
Dr. Sakamoto and Dr. Weissman at Stanford University have been working on a novel treatment for malignant tumors in children, with a focus on pediatric brain tumors. The team recently completed preclinical experiments on Hu5F9-G4, an innovative treatment that harnesses the body’s own immune system to fight cancer. Their recent experiments used various different models of childhood cancers, including five different solid tumor types, and two leukemias, to test this treatment. Their studies evaluated whether the treatment was effective, the potential side effects, and the appropriate dose.
The studies with Hu5F9-G4, the anti-CD47 treatment, are highly promising. The treatment reduced the size of tumors without significant side effects. Stanford has recently started an adult clinical trial for test the safety of Hu5F9-G4 in cancer patients. Dr. Sakamoto’s hope was to initiate the pediatric clinical trial for brain tumors later in 2015, however the pediatric trial has been put on hold until the adult trial is complete. The results of the adult trial will show if the drug is safe in adults and this information is needed before a drug can be tested in children. To accelerate the delivery of this treatment to children, the adult trial will soon enroll older pediatric patients (ages 18+). Dr. Sakamoto is encouraged that the pediatric trial will be carried out late in 2016. If successful, they also hope to develop a parallel clinical trial for AML patients using the anti-CD47 antibody.