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Imaging‐guided therapy simultaneously targeting HER2 and EpCAM with trastuzumab and EpCAM‐directed toxin provides additive effect in Ovarian cancer model

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dc.contributor.authorXu, T.
dc.contributor.authorVorobyeva, A.
dc.contributor.authorSchulga, A.
dc.contributor.authorKonovalova, E.
dc.contributor.authorDeyev, S. M.
dc.contributor.authorДеев, Сергей Михайлович
dc.date.accessioned2024-11-29T18:12:00Z
dc.date.available2024-11-29T18:12:00Z
dc.date.issued2021
dc.description.abstract© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co‐targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2‐positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2‐targeting component. As the EpCAM‐targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1‐LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1‐LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM‐ and HER2‐expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co‐treatment using Ec1‐LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1‐LoPE was well tolerated without signs of hepatic or kidney toxicity. Co‐treatment with trastuzumab and Ec1‐LoPE might be a potential therapeutic strategy for HER2‐ and EpCAM‐positive OC.
dc.identifier.citationImaging‐guided therapy simultaneously targeting HER2 and EpCAM with trastuzumab and EpCAM‐directed toxin provides additive effect in Ovarian cancer model / Xu, T. [et al.] // Cancers. - 2021. - 13. - № 16. - 10.3390/cancers13163939
dc.identifier.doi10.3390/cancers13163939
dc.identifier.urihttps://www.doi.org/10.3390/cancers13163939
dc.identifier.urihttps://www.scopus.com/record/display.uri?eid=2-s2.0-85111653717&origin=resultslist
dc.identifier.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000688975100001
dc.identifier.urihttps://openrepository.mephi.ru/handle/123456789/24445
dc.relation.ispartofCancers
dc.titleImaging‐guided therapy simultaneously targeting HER2 and EpCAM with trastuzumab and EpCAM‐directed toxin provides additive effect in Ovarian cancer model
dc.typeArticle
dspace.entity.typePublication
oaire.citation.issue16
oaire.citation.volume13
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relation.isAuthorOfPublication.latestForDiscovery66f50b35-0e92-49e0-ad1a-0ac386d858b7
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