Dual targeting of cancer cells with darpin-based toxins for overcoming tumor escape

Elena Shramova, Galina Proshkina, Victoria Shipunova, Anastasia Ryabova, Roman Kamyshinsky, Andrey Konevega, Aleksey Schulga, Elena Konovalova, Georgij Telegin, Sergey Deyev

Research output: Contribution to journalArticlepeer-review

Abstract

We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins – a low immunogenic variant of Pseudomonas aeruginosa exotoxin A and ribonuclease Barnase from Bacillus amyloliquefaciens. The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins). We have shown that both target agents efficiently accumulate in the tumor. Simultaneous treatment of breast carcinoma-bearing mice with anti-EpCAM fusion toxin based on LoPE and HER2-specific liposomes loaded with Barnase leads to concurrent elimination of primary tumor and metastases. Monotherapy with anti-HER2-or anti-EpCAM-toxins did not produce a comparable effect on metastases. The proposed approach can be considered as a promising strategy for significant improvement of cancer therapy.

Original languageEnglish
Article number3014
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Barnase
  • Cancer therapy
  • EpCAM
  • HER2
  • Liposomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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