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Open AccessCommunication
Int. J. Mol. Sci. 2017, 18(2), 401; doi:10.3390/ijms18020401

A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-137 Wroclaw, Poland
2
Preclinical Development Department, R&D Celon Pharma Inc., 05-092 Lomianki/Kielpin, Poland
3
Department of Protein Biotechnology, Faculty of Biotechnology, University of Wroclaw, 50-137 Wroclaw, Poland
4
Research and Development Department, Pure Biologics Ltd., 54-427 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Ian A. Nicholls
Received: 14 December 2016 / Revised: 20 January 2017 / Accepted: 31 January 2017 / Published: 14 February 2017
(This article belongs to the Section Molecular Recognition)
View Full-Text   |   Download PDF [5344 KB, uploaded 14 February 2017]   |  

Abstract

Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in E. coli and purified by Ni-nitrilotriacetyl (Ni-NTA) agarose chromatography. The molecule was properly folded, and the high affinity and specificity of its interaction with HER2 was confirmed by surface plasmon resonance (SPR) and flow cytometry, respectively. The (ZHER2:4)2DCS-MMAE conjugate was obtained by coupling the maleimide group linked with MMAE to cysteines, which were introduced in a drug conjugation sequence (DCS). Cytotoxicity of the conjugate was evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT assay and the xCELLigence Real-Time Cell Analyzer. Our experiments demonstrated that the conjugate delivered auristatin E specifically to HER2-positive tumor cells, which finally led to their death. These results indicate that the cytotoxic diaffibody conjugate is a highly potent molecule for the treatment of various types of cancer overexpressing HER2 receptors. View Full-Text
Keywords: targeted therapy; HER2; diaffibody; monomethyl auristatin E (MMAE) targeted therapy; HER2; diaffibody; monomethyl auristatin E (MMAE)
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MDPI and ACS Style

Serwotka-Suszczak, A.M.; Sochaj-Gregorczyk, A.M.; Pieczykolan, J.; Krowarsch, D.; Jelen, F.; Otlewski, J. A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells. Int. J. Mol. Sci. 2017, 18, 401.

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