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HER2-Specific Targeted Toxin DARPin-LoPE: Immunogenicity and Antitumor Effect on Intraperitoneal Ovarian Cancer Xenograft Model

1
Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., Nizhny Novgorod 603950, Russia
2
Laboratory of Molecular Immunology, Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 16/10 Miklukho-Maklay St., Moscow 117997, Russia
3
Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya str., Moscow 119991, Russia
4
Research Nuclear Reactor Center, National Research Tomsk Polytechnic University, 30 Lenin ave., Tomsk 634050, Russia
5
Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University “MEPhI”, 31 Kashirskoe Shosse, Moscow 115409, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2399; https://doi.org/10.3390/ijms20102399
Received: 8 April 2019 / Revised: 4 May 2019 / Accepted: 14 May 2019 / Published: 15 May 2019
(This article belongs to the Section Biochemistry)
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Abstract

High immunogenicity and systemic toxicity are the main obstacles limiting the clinical use of the therapeutic agents based on Pseudomonas aeruginosa exotoxin A. In this work, we studied the immunogenicity, general toxicity and antitumor effect of the targeted toxin DARPin-LoPE composed of HER2-specific DARPin and a low immunogenic exotoxin A fragment lacking immunodominant human B lymphocyte epitopes. The targeted toxin has been shown to effectively inhibit the growth of HER2-positive human ovarian carcinoma xenografts, while exhibiting low non-specific toxicity and side effects, such as vascular leak syndrome and liver tissue degradation, as well as low immunogenicity, as was shown by specific antibody titer. This represents prospects for its use as an agent for targeted therapy of HER2-positive tumors. View Full-Text
Keywords: targeted therapy; DARPin; Pseudomonas exotoxin A; immunogenicity; ovarian carcinoma; HER2; far-red fluorescent protein targeted therapy; DARPin; Pseudomonas exotoxin A; immunogenicity; ovarian carcinoma; HER2; far-red fluorescent protein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Sokolova, E.A.; Shilova, O.N.; Kiseleva, D.V.; Schulga, A.A.; Balalaeva, I.V.; Deyev, S.M. HER2-Specific Targeted Toxin DARPin-LoPE: Immunogenicity and Antitumor Effect on Intraperitoneal Ovarian Cancer Xenograft Model. Int. J. Mol. Sci. 2019, 20, 2399.

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