| Literature DB >> 28898695 |
Kristopher R Bosse1, Pichai Raman2, Zhongyu Zhu3, Maria Lane4, Daniel Martinez5, Sabine Heitzeneder6, Komal S Rathi2, Nathan M Kendsersky4, Michael Randall4, Laura Donovan7, Sorana Morrissy7, Robyn T Sussman4, Doncho V Zhelev3, Yang Feng3, Yanping Wang3, Jennifer Hwang3, Gonzalo Lopez4, Jo Lynne Harenza4, Jun S Wei8, Bruce Pawel5, Tricia Bhatti5, Mariarita Santi5, Arupa Ganguly9, Javed Khan8, Marco A Marra10, Michael D Taylor7, Dimiter S Dimitrov3, Crystal L Mackall11, John M Maris12.
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.Entities:
Keywords: MYCN; antibody-drug conjugate; glypican; immunotherapy; medulloblastoma; neuroblastoma
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Year: 2017 PMID： 28898695 PMCID： PMC5600520 DOI： 10.1016/j.ccell.2017.08.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585