A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma
文献类型：期刊论文
| 作者 | Zhao, Qi; Tran, Hoa; Dimitrov, Dimiter S.; Cheung, Nai-Kong V. |
| 刊名 | INTERNATIONAL JOURNAL OF CANCER
 |
| 出版日期 | 2015 |
| 英文摘要 | The insulin-like growth factors (IGFs), IGF-1 and IGF-2, have been implicated in the growth, survival and metastasis of a broad range of malignancies including pediatric tumors. They bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR) which are overexpressed in many types of solid malignancies. Activation of the IR by IGF-2 results in increased survival of tumor cells. We have previously identified a novel human monoclonal antibody, m708.5, which binds with high (pM) affinity to both human IGF-1 and IGF-2, and potently inhibits phosphorylation of the IGF-1R and the IR in tumor cells. m708.5 exhibited strong antitumor activity as a single agent against most cell lines derived from neuroblastoma, Ewing family of tumor, rhabdomyosarcoma and osteosarcoma. When tested in neuroblastoma cell lines, it showed strong synergy with temsirolimus and synergy withchemotherapeutic agents in vitro. In xenograft models, the combination of m708.5 and temsirolimus significantly inhibited neuroblastoma growth and prolonged mouse survival. Taken together, these results support the clinical development of m708.5 for pediatric solid tumors with potential for synergywith chemotherapy and mTOR inhibitors. What's new? Insulin-like growth factors (IGF) 1 and 2 promote the biogenesis of neuroblastoma, a frequent neuroendocrine tumor in early childhood. Here the authors show that targeting IGF-1 and 2 with a specific antibody (m708.5) has anti-tumor activity in neuroblastoma cell lines as well as in cell culture models of the Ewing family of tumors, rhabdomyosarcoma, and osteosarcoma. Similarly, in xenograft mouse models of neuroblastoma, m798.5 together with an inhibitor of mammalian target of rapamycin (mTOR) suppressed tumor growth and increased survival, supporting a potential clinical application of antibodies targeting IGF-1/2 in children afflicted with solid tumors. |
| 收录类别 | SCI |
| 原文出处 | http://onlinelibrary.wiley.com/doi/10.1002/ijc.29588/full |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/7327]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 作者单位 | INTERNATIONAL JOURNAL OF CANCER |
| 推荐引用方式 GB/T 7714 | Zhao, Qi,Tran, Hoa,Dimitrov, Dimiter S.,et al. A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma[J]. INTERNATIONAL JOURNAL OF CANCER,2015. |
| APA | Zhao, Qi,Tran, Hoa,Dimitrov, Dimiter S.,&Cheung, Nai-Kong V..(2015).A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma.INTERNATIONAL JOURNAL OF CANCER. |
| MLA | Zhao, Qi,et al."A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma".INTERNATIONAL JOURNAL OF CANCER (2015). |
入库方式： OAI收割
来源：深圳先进技术研究院
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