{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T19:08:48Z","timestamp":1768590528236,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009550","name":"Hasselt University","doi-asserted-by":"publisher","award":["G.0581.12N"],"award-info":[{"award-number":["G.0581.12N"]}],"id":[{"id":"10.13039\/501100009550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009550","name":"Hasselt University","doi-asserted-by":"publisher","award":["AUHL\/15\/2-GOH3816N"],"award-info":[{"award-number":["AUHL\/15\/2-GOH3816N"]}],"id":[{"id":"10.13039\/501100009550","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation Flanders","award":["G.0581.12N"],"award-info":[{"award-number":["G.0581.12N"]}]},{"name":"Research Foundation Flanders","award":["AUHL\/15\/2-GOH3816N"],"award-info":[{"award-number":["AUHL\/15\/2-GOH3816N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ovarian cancer ranks fifth in cancer-related deaths among women. Since ovarian cancer patients are often asymptomatic, most patients are diagnosed only at an advanced stage of disease. This results in a 5-year survival rate below 50%, which is in strong contrast to a survival rate as high as 94% if detected and treated at an early stage. Monitoring serum biomarkers offers new possibilities to diagnose ovarian cancer at an early stage. In this study, nanobodies targeting the ovarian cancer biomarkers human epididymis protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), and progranulin (PGRN) were evaluated regarding their expression levels in bacterial systems, epitope binning, and antigen-binding affinity by enzyme-linked immunosorbent assay and surface plasmon resonance. The selected nanobodies possess strong binding affinities for their cognate antigens (KD~0.1\u201310 nM) and therefore have a pronounced potential to detect ovarian cancer at an early stage. Moreover, it is of utmost importance that the limits of detection (LOD) for these biomarkers are in the pM range, implying high specificity and sensitivity, as demonstrated by values in human serum of 37 pM for HE4, 163 pM for SLPI, and 195 pM for PGRN. These nanobody candidates could thus pave the way towards multiplexed biosensors.<\/jats:p>","DOI":"10.3390\/ijms232213687","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T08:52:56Z","timestamp":1667897576000},"page":"13687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Nanobodies for the Early Detection of Ovarian Cancer"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8450-3793","authenticated-orcid":false,"given":"Lan-Huong","family":"Tran","sequence":"first","affiliation":[{"name":"Biomolecule Design Group, Institute for Materials Research (IMO-IMOMEC), Hasselt University, Agoralaan-Building D, BE-3590 Diepenbeek, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-3396","authenticated-orcid":false,"given":"Geert-Jan","family":"Graulus","sequence":"additional","affiliation":[{"name":"Biomolecule Design Group, Institute for Materials Research (IMO-IMOMEC), Hasselt University, Agoralaan-Building D, BE-3590 Diepenbeek, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-7444","authenticated-orcid":false,"given":"C\u00e9cile","family":"Vincke","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, BE-1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Smiejkowska","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biochemistry, University of Antwerp, Prinsstraat 13, BE-2000 Antwerpen, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Kindt","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, BE-1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-4833","authenticated-orcid":false,"given":"Nick","family":"Devoogdt","sequence":"additional","affiliation":[{"name":"In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Pleinlaan 2, BE-1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-3575","authenticated-orcid":false,"given":"Serge","family":"Muyldermans","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, BE-1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-0150","authenticated-orcid":false,"given":"Peter","family":"Adriaensens","sequence":"additional","affiliation":[{"name":"Biomolecule Design Group, Institute for Materials Research (IMO-IMOMEC), Hasselt University, Agoralaan-Building D, BE-3590 Diepenbeek, Belgium"},{"name":"Analytical and Circular Chemistry, Institute for Materials Research (IMO-IMOMEC), Hasselt University, Agoralaan-Building D, BE-3590 Diepenbeek, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8709-9856","authenticated-orcid":false,"given":"Wanda","family":"Guedens","sequence":"additional","affiliation":[{"name":"Biomolecule Design Group, Institute for Materials Research (IMO-IMOMEC), Hasselt University, Agoralaan-Building D, BE-3590 Diepenbeek, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1166\/jbn.2015.2063","article-title":"Anti-mesothelin nanobodies for both conventional and nanoparticle-based biomedical applications","volume":"11","author":"Prantner","year":"2015","journal-title":"J. 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