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首页> 外文期刊>Journal of Cellular Physiology >Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors
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Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors

机译：小说anti-ErbB3单克隆抗体在异种移植和治疗效果自发的老鼠肿瘤

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The role of the ErbB3 receptor in signal transduction is to augment the signaling repertoire of active heterodimeric ErbB receptor complexes through activating the PI3K/AKT pathway, which in turn promotes survival and proliferation. ErbB3 has recently been proposed to be involved in acquired resistance to tyrosine kinase inhibitors (TKIs), and is therefore a promising new drug cancer target. Since ErbB3 is a kinase defective receptor, it cannot be targeted by small molecule inhibitors, whereas monoclonal antibodies may offer a viable strategy for pharmacological intervention. In this study, we have utilized DNA electroporation (DNA-EP) to generate a set of novel hybridomas directed against human ErbB3, which have been characterized for their biochemical and functional properties and selected for their ability to negatively regulate the ErbB3-mediated signaling pathway. In vitro, the anti-ErbB3 antibodies modulate the growth rate of cancer cells of different origins. In vivo they show antitumoral properties in a xenograft model of human pancreatic tumor and in the ErbB2-driven carcinogenesis genetically engineered mouse model (GEMM) for mammary tumor, the BALB/neuT. Our data confirm that downregulating the ErbB3-mediated signals with the use of anti-ErbB3 monoclonal antibodies is both feasible and relevant for therapeutic purposes and provides new opportunities for novel anti-ErbB3 combinatory strategies for cancer treatment. J. Cell. Physiol. 227: 3381-3388, 2012.
机译：ErbB3的作用受体信号增强信号转导曲目的活跃heterodimeric ErbB受体通过激活PI3K / AKT复合物通路,进而促进生存和扩散。参与获得性耐药酪氨酸激酶抑制剂(TKIs),因此一个有前景的新癌症药物的目标。激酶受体缺陷,它不能小分子抑制剂的目标,而单克隆抗体可能会提供一个可行的策略药理干预。我们利用DNA电穿孔(DNA-EP)杂种细胞直接生成一组的小说对人类ErbB3生化和特点功能属性和选择负调节ErbB3-mediated能力信号通路。抗体调节癌症的增长速度细胞不同的起源。antitumoral异种移植模型的属性人类胰腺肿瘤和ErbB2-driven致癌基因工程小鼠模型(GEMM)乳腺肿瘤,BALB /中性粒细胞。确认ErbB3-mediated表达下调信号使用anti-ErbB3单克隆抗体是可行的和相关的治疗的目的,提供了新的小说的机会anti-ErbB3组合癌症治疗的策略。杂志。227:3381 - 3388年,2012年。

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