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

  1. Author:
    Bosse, Kristopher R
    Raman, Pichai
    Zhu, Zhongyu
    Lane, Maria
    Martinez, Daniel
    Heitzeneder, Sabine
    Rathi, Komal S
    Kendsersky, Nathan M
    Randall, Michael
    Donovan, Laura
    Morrissy, Sorana
    Sussman, Robyn T
    Zhelev, Doncho V
    Feng, Yang
    Wang, Yanping
    Hwang, Jennifer
    Lopez, Gonzalo
    Harenza, Jo Lynne
    Wei, Jun S
    Pawel, Bruce
    Bhatti, Tricia
    Santi, Mariarita
    Ganguly, Arupa
    Khan, Javed
    Marra, Marco A
    Taylor, Michael D
    Dimitrov, Dimiter
    Mackall, Crystal L
    Maris, John M

  2. Author Address

    Division of Oncology and Center for Childhood Cancer Research, Children 39;s Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Division of Oncology and Center for Childhood Cancer Research, Children 39;s Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics and Center for Data-Driven Discovery in Biomedicine, Children 39;s Hospital of Philadelphia, Philadelphia, PA 19104, USA., Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21701, USA., Division of Oncology and Center for Childhood Cancer Research, Children 39;s Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA., Department of Pathology, Children 39;s Hospital of Philadelphia, Philadelphia, PA 19104, USA., Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA., Division of Neurosurgery and the Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Genome Sciences Center, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada., Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA., Division of Oncology and Center for Childhood Cancer Research, Children 39;s Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: maris@chop.edu.,
    1. Year: 2017
    2. Date: Sep 11
  2. Journal: Cancer Cell
    1. 32
    2. 3
    3. Pages: 295-309.e12
  4. Type of Article: Article
  5. Article Number: 295-309.e12
  1. Abstract:

    We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2017.08.003
  3. PMID: 28898695
  4. PMCID: PMC5600520
  5. View record in Web of Science®
  6. WOS: 000410199600007

Library Notes

  1. Fiscal Year: FY2016-2017
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