“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.
30 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 5 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 testing the safety of Hu5F9-G4 in cancer patients. Dr Sakamoto’s team hoped to initiate the pediatric clinical trial for brain tumors 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. So far, the adult trial is progressing well. The team is testing increasing amounts of the treatment to find the maximum tolerated dose (MTD) where the side effects are minimized. The adult trial is due to be completed in early 2016. To accelerate the delivery of this treatment to children, the adult trial is actively recruiting adolescent and young adult patients (AYA; ages 18+). To move towards testing the CD47 antibody in children, the AYA cohort will provide important information regarding the safety of the treatment in a younger group of patients. Drs. Sakamoto and Weissman hope that these studies will pave the way for a pediatric trial to be carried out in late 2016. If the current studies are successful, they will be able to test CD47 targeted therapy in several different pediatric tumors.
CureSearch is excited about this project, but unfortunately we are unable to provide additional funding support as of April 2016. This decision was weighed carefully and thoughtfully by the Scientific Advisory Council (SAC). The SAC had concerns that the timeline for initiating the pediatric clinical trial would not be met. CureSearch takes seriously our commitment to accountability and transparency. More importantly, we want to fund research that has the greatest opportunity to save children by reaching clinical trials within three years. CureSearch and the SAC remain excited and committed to the advancement of the CD47 immunotherapy. This is a pivotal study that promises to have a major therapeutic impact on a broad range of pediatric cancers. As such, we encouraged Dr. Sakamoto’s team to reapply for funding when they near the launch of the pediatric clinical trial.