Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Oct 21

PMID 33081407

Citations 22

Authors

Elena Shramova

Galina Proshkina

Victoria Shipunova

Anastasia Ryabova

Roman Kamyshinsky

Andrey Konevega

Aleksey Schulga

Elena Konovalova

Georgij Telegin

Sergey Deyev

Affiliations

Soon will be listed here.

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 exotoxin A and ribonuclease Barnase from . 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.

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