Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.,Cancer Cell

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.
Cancer Cell ( IF 50.3 ) Pub Date : 2017-09-11 , DOI: 10.1016/j.ccell.2017.08.003
Kristopher R Bosse ₁ , Pichai Raman ₂ , Zhongyu Zhu ₃ , Maria Lane ₄ , Daniel Martinez ₅ , Sabine Heitzeneder ₆ , Komal S Rathi ₂ , Nathan M Kendsersky ₄ , Michael Randall ₄ , Laura Donovan ₇ , Sorana Morrissy ₇ , Robyn T Sussman ₄ , Doncho V Zhelev ₃ , Yang Feng ₃ , Yanping Wang ₃ , Jennifer Hwang ₃ , Gonzalo Lopez ₄ , Jo Lynne Harenza ₄ , Jun S Wei ₈ , Bruce Pawel ₅ , Tricia Bhatti ₅ , Mariarita Santi ₅ , Arupa Ganguly ₉ , Javed Khan ₈ , Marco A Marra ₁₀ , Michael D Taylor ₇ , Dimiter S Dimitrov ₃ , Crystal L Mackall ₁₁ , John M Maris ₁

Affiliation

Division of Oncology and Center for Childhood Cancer Research, Children'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'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'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's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Department of Pathology, Children'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.

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.

中文翻译：

将 GPC2 鉴定为高危神经母细胞瘤的癌蛋白和候选免疫治疗靶点。

我们开发了一种基于 RNA 测序的管道，以发现神经母细胞瘤中差异表达的细胞表面分子，这些分子符合最佳免疫治疗靶标安全性和有效性的标准。在这里，我们表明 GPC2 是这种儿童癌症中强有力的候选免疫治疗靶点。由于 MYCN 转录激活和/或 GPC2 基因座的体细胞增益，我们证明了神经母细胞瘤中 GPC2 的高表达。我们确认 GPC2 在大多数神经母细胞瘤中高度表达，但在正常儿童组织中检测不到明显水平。此外，我们证明 GPC2 是神经母细胞瘤增殖所必需的。最后，我们开发了一种针对 GPC2 的抗体-药物偶联物，该偶联物对表达 GPC2 的神经母细胞瘤细胞具有很强的细胞毒性。集体，

更新日期：2017-09-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>