Publication:
Epithelial cell adhesion molecule-targeting designed ankyrin repeat protein-toxin fusion Ec1-LoPE exhibits potent cytotoxic action in prostate cancer cells

Дата
2022
Авторы
Xu, T.
Liu, Y.
Schulga, A.
Konovalova, E.
Deyev, S. M.
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Научные группы
Организационные подразделения
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Организационная единица
Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
Выпуск журнала
Аннотация
© 2022 Spandidos Publications. All rights reserved.Targeted anticancer therapeutics offer the advan- tage of reducing cytotoxic side effects to normal cells by directing the cytotoxic payload selectively to cancer cells. Designed ankyrin repeat proteins (DARPins) are promising non-immunoglobulin-based scaffold proteins for payload delivery to cancer-associated molecular targets. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 40-60% of prostate cancers (PCs) and is associated with metastasis, increased risk of PC recurrence and resistance to treatment. Here, we investigated the use of DARPin Ec1 for targeted delivery of Pseudomonas exotoxin A variant (LoPE) with low immunogenicity and low non-specific toxicity to EpCAM-expressing prostate cancer cells. Ec1-LoPE fusion protein was radiolabeled with tricarbonyl technetium-99m and its binding specificity, binding kinetics, cellular processing, internalization and cytotoxicity were evaluated in PC-3 and DU145 cell lines. Ec1-LoPE showed EpCAM-specific binding to EpCAM-expressing prostate cancer cells. Rapid internal- ization mediated potent cytotoxic effect with picomolar IC50values in both studied cell lines. Taken together, these data support further evaluation of Ec1-LoPE in a therapeutic setting in a prostate cancer model in vivo.
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Epithelial cell adhesion molecule-targeting designed ankyrin repeat protein-toxin fusion Ec1-LoPE exhibits potent cytotoxic action in prostate cancer cells / Xu, T. [et al.] // Oncology Reports. - 2022. - 47. - № 5. - 10.3892/or.2022.8305
URI
https://www.doi.org/10.3892/or.2022.8305
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85126872315&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000783665900001
 https://openrepository.mephi.ru/handle/123456789/28009
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