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Open Access Research article

Arg9 facilitates the translocation and downstream signal inhibition of an anti-HER2 single chain antibody

Yi Hu12, Chunxia Qiao2, Ming Lv2, Jiannan Feng2, Ming Yu2, Beifen Shen2, Qiuping Zhang13* and Yan Li24*

Author Affiliations

1 Department of Immunology, School of Basic Medical ScienÎ, Wuhan University, Wuhan, 430071, China

2 Laboratory of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, 100850, China

3 Department of Immunology, School of Basic Medical Science, Wuhan University, Donghu Road #185, Wuchang, Wuhan, 430071, China

4 Laboratory of Molecular Immunology, Institute of Basic Medical Sciences, P.O. Box 130(3), Taiping Road #27, Beijing, 100850, China

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BMC Research Notes 2012, 5:336  doi:10.1186/1756-0500-5-336

Published: 2 July 2012

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