A targeted toxin based on a binding module of non-immunoglobulin scaffold as a new agent for theranostics

Galina M. Proshkina, O. A. Stremovskiy, D. V. Sibrikova, A. V. Ryabova, S. M. Deyev

Research output: Contribution to journalArticle

Abstract

The aim of the investigation was to create multifunctional antitumor protein agent DARPin-mCherry-PE40 possessing both diagnostic and therapeutic properties. Materials and Methods. The experiments were carried out on human cell lines of breast adenocarcinoma SK-BR-3. Chinese hamster ovarian cell line CHO-K1 was used as a control. Genetic engineering methods, metal chelate affinity chromatography, confocal microscopy and spectrophotometric MTT test were used to perform the experiments. Results. A multifunctional targeted anticancer protein agent DARPin-mCherry-PE40 consisting of targeted HER2-specific nonimmunoglobulin module DARPin, an imaging module mCherry and cytotoxic module based on a fragment of Pseudomonas exotoxin A (PE40) has been created. Using HER2-positive cells it was shown in vitro that all three domains of the recombinant protein retained their functional qualities — high affinity for HER2 antigen, ability to fluorescence, and cytotoxicity. Conclusion. The ability of the targeted antitumor agent DARPin-mCherry-PE40 selectively stains HER2-positive cells and highly selective cytotoxicity against these cells make this targeted recombinant protein DARPin-mCherry-PE40 a perspective theranostic agent for the diagnosis and treatment of HER2-positive human tumors.

Original languageEnglish
Pages (from-to)7-12
Number of pages6
JournalSovremennye Tehnologii v Medicine
Volume8
Issue number4
DOIs
Publication statusPublished - 2016

Fingerprint

Immunotoxins
Scaffolds
Antineoplastic Agents
Cells
Recombinant Proteins
Cytotoxicity
Cell Line
Genetic Engineering
Cricetulus
Affinity Chromatography
Affinity chromatography
Genetic engineering
Confocal Microscopy
Confocal microscopy
Proteins
Adenocarcinoma
Breast
Coloring Agents
Fluorescence
Metals

Keywords

  • DARPin
  • HER2 receptor
  • MCherry
  • PE40
  • Pseudomonas aeruginosa exotoxin A fragment
  • Theranostics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A targeted toxin based on a binding module of non-immunoglobulin scaffold as a new agent for theranostics. / Proshkina, Galina M.; Stremovskiy, O. A.; Sibrikova, D. V.; Ryabova, A. V.; Deyev, S. M.

In: Sovremennye Tehnologii v Medicine, Vol. 8, No. 4, 2016, p. 7-12.

Research output: Contribution to journalArticle

Proshkina, Galina M. ; Stremovskiy, O. A. ; Sibrikova, D. V. ; Ryabova, A. V. ; Deyev, S. M. / A targeted toxin based on a binding module of non-immunoglobulin scaffold as a new agent for theranostics. In: Sovremennye Tehnologii v Medicine. 2016 ; Vol. 8, No. 4. pp. 7-12.
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