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Int. J. Mol. Sci. 2017, 18(8), 1688; doi:10.3390/ijms18081688

Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
2
Department of Protein Biotechnology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Received: 29 June 2017 / Revised: 27 July 2017 / Accepted: 31 July 2017 / Published: 3 August 2017
(This article belongs to the Special Issue Tumor Targeting Therapy and Selective Killing)
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Abstract

In our previous work we demonstrated that a small protein called affibody can be used for a cytotoxic conjugate development. The anti-HER2 affibody was armed with one moiety of a highly potent auristatin E and specifically killed HER2-positive cancer cells with a nanomolar IC50. The aim of this study was to improve the anti-HER2 affibody conjugate by increasing its size and the number of conjugated auristatin molecules. The affibody was fused to the Fc fragment of IgG1 resulting in a dimeric construct with the molecular weight of 68 kDa, referred to as ZHER2:2891-Fc, ensuring its prolonged half-life in the blood. Due to the presence of four interchain cysteines, the fusion protein could carry four drug molecules. Notably, the in vitro tests of the improved anti-HER2 conjugate revealed that it exhibits the IC50 of 130 pM for the HER2-positive SK-BR-3 cells and 98 nM for the HER2-negative MDA-MB-231 cells. High efficacy and specificity of the auristatin conjugate based on ZHER2:2891-Fc indicate that this construct is suitable for further in vivo evaluation. View Full-Text
Keywords: affibody; HER2; Fc fragment of IgG1; monomethyl auristatin E (MMAE) affibody; HER2; Fc fragment of IgG1; monomethyl auristatin E (MMAE)
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MDPI and ACS Style

Sochaj-Gregorczyk, A.M.; Ludzia, P.; Kozdrowska, E.; Jakimowicz, P.; Sokolowska-Wedzina, A.; Otlewski, J. Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1. Int. J. Mol. Sci. 2017, 18, 1688.

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