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Antibody-Drug Conjugate Could Lead to Treatment Advances in Pediatric Neuroblastoma

Brandon Scalea
Published: Monday, Aug 13, 2018

Kristopher R. Bosse, MD,

Kristopher R. Bosse, MD

An antibody-drug conjugate targeting the GPC2 molecule could have potential in pediatric patients with neuroblastoma, according to recent preclinical data.

The lead investigator of the study, Kristopher R. Bosse, MD, said this could be a breakthrough in the field, because identifying molecular targets has proven difficult in neuroblastoma.

In an interview with OncLive, Bosse, a pediatric oncologist at the Children’s Hospital of Philadelphia, discussed how D3-GPC2-PBD could impact pediatric neuroblastoma.

OncLive: Please provide some background to this study.

Bosse: We used a large sequencing data set to identify differently expressed genes in neuroblastoma and not normal tissues. This molecule, called GPC2, was identified in this approach. We built a very potent antibody-drug conjugate, where we pick a specific GPC2 antibody and link it to a DNA-damaging drug. The antibody is selectively targeted to this tumor by this molecule, then it's taken up into the cells and the drug is released. The tumors eventually will die.

What were the results with this agent and what are the clinical implications?

The abstract we presented here is a continuation of this work and using this antibody-drug conjugate in a panel of neuroblastoma patient-derived xenografts that differ in both their expression of this molecule and their genomic characteristics that are common in neuroblastoma. What we found is that the antibody-drug conjugate is effective across this panel, both in neuroblastoma and other cancers that express this molecule. It's the basis of preclinical work that we hope to now build into a clinical trial.

What are the next steps?

We're working with several companies and view this as a tool compound. We need to still work with this antibody and other drugs and find out what the best combination is. We can look at it in neuroblastoma and other cancers.

What do you think about the current state of therapy in pediatric cancer?

In pediatric and adult cancers, we are all really excited about immunotherapy. In pediatrics, when we think about immunotherapy, we're really talking about antibody-based therapies, antibody-drug conjugates, or CAR T cells. What we are learning in pediatrics is that there's a lot of molecules we've yet to discover, and GPC2 is one of the first that we've really gone from discovery to new therapies. We're pretty excited about that. There's a lot of molecules that we're yet to begin to explore. This is just the tip of the iceberg.
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