A dual‐specific anti‐IGF‐1/IGF‐2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma

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	A dual‐specific anti‐IGF‐1/IGF‐2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma
	Zhao, Q.; Tran, H.; Dimitrov, D.; Cheung, N.
	2015-11-01
Source Publication	International Journal of Cancer
ISSN	0020-7136
Pages	2243-2252
Abstract	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 with chemotherapeutic 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 synergy with chemotherapy and mTOR inhibitors.
Keyword	IGF-1 IGF-2 chemotherapy neuroblastoma temsirolimus
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	55324
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Cheung, N.
Recommended Citation GB/T 7714	Zhao, Q.,Tran, H.,Dimitrov, D.,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, 2243-2252.
APA	Zhao, Q.., Tran, H.., Dimitrov, D.., & Cheung, N. (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, 2243-2252.
MLA	Zhao, Q.,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):2243-2252.

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