Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma

   It has been discovered, that GPC2 is expressed at high levels on most neuroblastomas (NB) but not appreciable levels in normal childhood tissues and that GPC2 is critical for NB maintenance.

Picture 1

   GPC2 is localized on chromosome 7q22.1, which is somatically gained in approximately 40% of high-risk primary neuroblastoma tumors, typically either as entire chromosome 7 or chromosome arm 7q gain (Picture 1).

Picture 2
GPC2 immunofluorescence stainig 
in the neuroblastoma

 Although not as well defined as a prognostic marker as other acquired segmental chromosomal aberrations in primary neuroblastomas, somatic gain of chromosome 7 is a frequent and potentially biologically relevant event in neuroblastoma tumorigenesis.
   Plasma membrane localized GPC2 is expressed in a majority of High-Risk Neuroblastomas.
   GPC2 expression is restricted in normal tissues. To be a safe immunotherapeutic target, a cell-surface molecule must have limited cell-surface expression on normal human tissues. In addition, in pediatric cancers, special attention to normal childhood tissues is critical for these embryonal neoplasms that deregulate developmental pathways. So, GPC2 mRNA expression is highly restricted in normal human tissues, including normal neural crest cells.
   A GPC2 Targeting Antibody-Drug Conjugate (ADS) is cytotoxic to GPC2-expressing neuroblastoma cells. (Picture 3).

Picture 3

 









Source of information: "CellPress", Cancer Cell 32, 295 - 309, September 11, 2017 (full article)
http://dx.doi.org/10.1016/j.ccell.2017.08.003