Researchers Find Immunotherapy Target for Neuroblastoma

An effective treatment for high-risk pediatric cancer may be on the horizon following the discovery of a potential target for immunotherapy. In both cell and animal models, a chemotherapy-antibody combination was found to target neuroblastoma cells, according to a study published at Cancer Cell.

“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,” said researcher John M. Maris, MD. “Furthermore, our findings may also lend support to the development of other immune-based therapies, such as CAR T-cells, in children with multiple aggressive cancers, in addition to neuroblastoma.”

Neuroblastoma affects developing peripheral nervous system that presents as a tumor in the chest or abdomen in pediatric patients. This cancer is common among infants and can be aggressive, resulting in a significant amount of pediatric cancer deaths.

In the study, the authors discovered molecules that are common on the surface of neuroblastoma cells but not common on healthy cells.

“Our rationale was to identify a cell-surface molecule that an immune-based therapy could target without damaging healthy tissues,” said lead researcher and first author Kristopher R. Bosse, MD. “Using this approach, we identified a protein called glypican-2, or GPC2.”

GPC2 is a cell-surface protein that communicates with growth factors and receptors, which play a role in intracellular signaling pathways. The authors also found that GPC2 is crucial for the proliferation of neuroblastoma cells.

These findings suggest that GPC2 may kill cancer cells, not affect healthy cells, and hinder the ability of cancer cells to become resistant to immunotherapy, according to the study.

“Given GPC2’s critical role in the growth of neuroblastomas, we hope that tumors will not be able to simply downregulate this protein in order to escape recognition by our immunotherapies that target GPC2,” Dr Bosse said.

After identifying GPC2 as a target for neuroblastoma, the authors developed an antibody-drug conjugate (ADC).

The drug, D3-GPC2-PBD, is a combination of an antibody that recognizes GPC2 and chemotherapy that is engulfed by cancer cells. This treatment targets DNA in tumors, while not affecting healthy cells, according to the study.

The authors found that the drug compound killed neuroblastoma cells but was not toxicity in healthy cells in both cell cultures and mouse models of the cancer, according to the study.

These results suggest that this novel therapy may effectively treat pediatric neuroblastoma.

“These findings establish that this type of immunotherapy could be potentially safe and effective against neuroblastoma,” Dr Maris said. “Our next steps will be to further evaluate this ADC and also develop other immune-based therapies directed against 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.”