10:37pm Tuesday 22 August 2017

Children's National Finds Neuroblastoma Tumor Cure in Mice Studies

Anthony Sandler, MD, Senior Vice President, the Joseph E. Robert, Jr., Center for Surgical Care, led the study that was published in PLOS ONE.

The work is part of a scientific effort to “advance cancer immunotherapy by understanding how cancer cells change their behavior and activate the immune system,” Dr. Sandler says.

The study is particularly significant because neuroblastoma, most commonly centered in the adrenal glands, is the third most common tumor in childhood, and the most common cancer in babies younger than one year old. It accounts for six percent of all childhood cancers in the United States, with about 700 children younger than 15 diagnosed each year.

“Historically, tumor vaccines held much promise, but demonstrated little clinical success,” Dr. Sandler and his team wrote. “Thus, the task of establishing an effective anti-tumor response in neuroblastoma has been daunting.” However, with this most recent study finding, Dr. Sandler says this failed promise is changing.

The study revealed that “knockdown'” of a DNA-protein inhibitor, known as ID-2, in aggressive high-risk solid tumors resulted in activation of T-cells, which are white blood cells that have figured significantly in immunity research. Gene knockdown refers to a technique in which the expression of one or more of a cell’s genes is reduced.

The research also focused on using “checkpoint blockade,” a therapy in clinical use that allows for expansion of the immune response against tumors. “The combination of selective gene knock-down in tumor cells and checkpoint blockade produced a novel, potent T-cell triggered tumor vaccine strategy,” Dr. Sandler says.

As Children’s researchers examined the impact of the knockdown of ID-2 protein on a tumor, they implanted N2a, a fast growing mouse neuroblastoma cell line, in the mice. Unexpectedly, Sandler said,

“Most of the mice rejected the tumor cells and subsequently were protected against further tumor challenges.”

The researchers also noted that a “massive influx” of T-cells infiltrated the shrinking tumor, indicating that T-cells are necessary for antitumor immunity in this vaccination protocol.

The researchers will be working toward potential clinical trials to make further progress in neuroblastoma research, with immunotherapy playing a key role, Dr. Sandler says. Dr. Sandler and his team noted that “strategies to circumvent treatment failures are intensively studied and amongst these strategies, immunotherapy has recently been revitalized and is attracting much attention.”

Dr. Sandler has been working on immunological research related to childhood cancers for more than 15 years.

 

 

Contact: Emily Hartman at 202-476-4500.

 

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About Children’s National Health System

 

Children’s National Health System, based in Washington, DC, has been serving the nation’s children since 1870. Children’s National is Magnet® designated, and was ranked among the top 10 pediatric hospitals by U.S. News & World Report 2015-16. Home to the Children’s Research Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National is one of the nation’s top NIH-funded pediatric institutions. With a community-based pediatric network, seven regional outpatient centers, an ambulatory surgery center, two emergency rooms, an acute care hospital, and collaborations throughout the region, Children’s National is recognized for its expertise and innovation in pediatric care and as an advocate for all children.


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