原创力文档arg9 facilitates the translocation and downstream signal inhibition of an anti-her2 single chain antibodyarg9促进的易位和下游信号抑制anti-her2单链抗体.pdfVIP
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arg9 facilitates the translocation and downstream signal inhibition of an anti-her2 single chain antibodyarg9促进的易位和下游信号抑制anti-her2单链抗体
Hu et al. BMC Research Notes 2012, 5:336
/1756-0500/5/336
RESEARCH ARTICLE Open Access
Arg9 facilitates the translocation and downstream
signal inhibition of an anti-HER2 single chain
antibody
1,2 2 2 2 2 2 1,3* 2,4*
Yi Hu , Chunxia Qiao , Ming Lv , Jiannan Feng , Ming Yu , Beifen Shen , Qiuping Zhang and Yan Li
Abstract
Background: HER2 plays a critical role in the pathogenesis of many cancers and is linked to poor prognosis or
cancer metastases. Monoclonal antibodies, such as Herceptin against HER2-overexpressing cancers, have showed
satisfactory clinical therapeutic effect. However, they have difficulty to surmount obstacles to enter cells or
blood–brain barrier.
Results: In this study, a cell-penetrating peptide Arg9 was linked to the C-terminus of anti-HER2 single chain
antibody (MIL5scFv). Flow cytometry, confocal microscopy and electron microscopy analysis all revealed that Arg9
peptide facilitated the penetration of MIL5scFv into HER2-negative cell line NIH3T3 and orientate in mitochondria.
More interestingly, Western blot assay showed the potential enhanced bioactivity of MIL5scFv-Arg9 in HER2+ cell
line SKOV3, indicating that Arg9 could help large molecules (e.g. antibody) to penetrate into cells and therefore
enhance its anti-neoplastic function.
Conclusions: Our work represented an attractive by preliminary strategy to enhance the therapeutic effect of
existing antibodies by entering cells easier, or more desirable, surmounting the physical barriers, especially in
hard-to-reach cancers such as brain metastases cases.
Keywords: HER2, Single chain antibody, Translocation
Background antibody such as si
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