New Data Reveals Potential Target for Neuroblastoma Treatment

Mathew Shanley

In the journal Cancer Cell, a study led by pediatric oncologists at the Children’s Hospital of Philadelphia (CHOP) was published in which a new immunotherapy target was identified for the potential treatment and prevention of neuroblastoma.

The study’s lead author Kristopher R. Bosse, MD and a team of scientists led by John M. Maris, MD initiated the study with the intention of evaluating the surface of neuroblastoma cells and discovering molecules that could serve as a target for treatments.

Second only to brain tumors, neuroblastoma is one of the most commonly-occurring solid tumors in childhood. In children under 5 years, neuroblastomas can develop anywhere that there is an existing group of nerve cells, or neuroblasts. The condition develops from immature neuroblasts found in a variety of areas throughout the body, and typically progresses in and around the adrenal glands, which rest above the kidneys.

The goal of the study was to detect a molecule on the cell-surface that could be targeted by an immune-based therapy while keeping healthy tissues undamaged, and an RNA-sequencing-based pipeline was developed to discover differentially expressed cell-surface molecules. RNA-sequencing data was compared in 126 high-risk primary neuroblastomas.

With this approach, a protein called glypican-2 (GPC2) was discovered and identified as necessary for the multiplication and expansion of tumor cells, making it a valid target. A drug that could kill GPC2 would overpower cancer cells, prevent them from spreading into metastasis, and successfully spare healthy cells.

Subsequently, Dr Bosse and colleagues developed antibody-drug conjugate (ADC), an antibody that can recognize GPC2 with a chemotherapy drug. It was tested in mouse models and human cell cultures and was found to successfully eliminate cancer cells with “no discernible toxicities.”

These findings establish that this type of immunotherapy could be potentially safe and effective,” said Dr Bosse to Medical News Today. “We have built a strong foundation for developing a completely new and hopefully much less toxic treatment for neuroblastoma, the most common cancer in infants."

Next steps include continued evaluation of the ADC, and the development of other similar immune-based therapies to fight GPC2.

"Because other glypicans in addition to GPC2 are overexpressed in other childhood cancers, it may also be possible to apply this approach across various types of high-risk pediatric cancers,” said Dr Maris.

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