Production of novel peptide-targeting antibodies for anti-Müllerian hormone receptor 2 and induction of cytotoxicity in ovarian cancer cells

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dc.contributor.authorSakalar, Cagri
dc.contributor.authorKurt, Busra
dc.contributor.authorSezen, Sedat
dc.contributor.authorKaya, Savas
dc.date.accessioned2025-02-22T14:08:52Z
dc.date.available2025-02-22T14:08:52Z
dc.date.issued2025
dc.departmentDicle Üniversitesien_US
dc.description.abstractOvarian cancer is generally diagnosed at late stages. Monoclonal antibodies (MAbs) targeting antigens in ovarian cancer are used in the clinic. Anti-M & uuml;llerian hormone receptor type 2 (AMHR2) is a receptor highly expressed in ovarian cancer and it is a potential target antigen for immunotherapy. Extracellular domain of AMHR2 was analysed in terms of 3D structure and physicochemical properties, and 3 peptide sequences (Peptides 1, 7 and 11) were determined as targets. MAb production protocol was performed, and 6 MAb clones showing high affinity for peptides were obtained. P3B1, P10A10, P10B6 and P2A6 clones were for peptide 11 (P11), P2C9 was for P7, and P6C5 was for P1. Antibody isotype of P2A6 was IgG2a and the others were of IgG1 isotype. MAb binding to the native recombinant protein (AMHR2-Fc) was analysed by enzyme-linked immunosorbent assay (ELISA) and MAb binding to AMHR2 expressed by SKOV-3 ovarian cancer cells was analysed by western blot and immunofluorescent staining. P3B1 showed strong, P10A10, P10B6 and P2C9 showed medium affinity for the native protein (AMHR2-Fc). P3B1 and P2C9 showed strong binding in western blot analysis. Clones showed moderate binding in immunoflorescent staining. A complement dependent cytotoxicity (CDC) experiment was conducted using MAbs and transfected SKOV-3 cells. P3B1 induced a significant CDC. Variable regions of P3B1 MAb were sequenced. In conclusion, MAbs for three different regions of AMHR2 were produced. One clone was shown to induce cytotoxicity in ovarian cancer cells and its sequence was determined for future use as a humanised therapeutic MAb.en_US
dc.description.sponsorshipBilimsel Arascedil;timath;rma Projeleri, Erciyes niversitesien_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUB & Idot;TAK), Grant Number: 113S322 (C. SAKALAR) and Erciyes University Scientific Research Fund (EU- BAP), Grant Number: TOA- 2014- 4877 (C. SAKALAR). We thank Prof. Beyhan Cengiz for his suggestions on the manuscriptr No Statement Availableen_US
dc.identifier.doi10.1111/sji.13426
dc.identifier.issn0300-9475
dc.identifier.issn1365-3083
dc.identifier.issue1en_US
dc.identifier.pmid39582305en_US
dc.identifier.scopus2-s2.0-85210006588en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1111/sji.13426
dc.identifier.urihttps://hdl.handle.net/11468/29685
dc.identifier.volume101en_US
dc.identifier.wosWOS:001361899700001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofScandinavian Journal of Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_WOS_20250222
dc.subjectanti-M & uuml;llerian hormone receptor type 2en_US
dc.subjectcomplement-dependent cytotoxicityen_US
dc.subjectmonoclonal antibodiesen_US
dc.subjectovarian canceren_US
dc.subjectpeptide targetsen_US
dc.titleProduction of novel peptide-targeting antibodies for anti-Müllerian hormone receptor 2 and induction of cytotoxicity in ovarian cancer cellsen_US
dc.typeArticleen_US

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