{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:39:35Z","timestamp":1770140375600,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T00:00:00Z","timestamp":1696723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["W1224"],"award-info":[{"award-number":["W1224"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High numbers of membrane immunoglobulin E (IgE)-positive cells are characteristic of allergic conditions, atopic dermatitis, or IgE myeloma. Antibodies targeting the extracellular membrane-proximal domain of the membranous IgE-B-cell receptor (BCR) fragment can be used for specific depletion of IgE-BCR-positive cells. In this study, we derivatized such an antibody with a toxin and developed an antibody\u2013drug conjugate (ADC) that showed strong cytotoxicity for an IgE-positive target cell line. Site-specific conjugation with maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl-auristatin E via a newly introduced single cysteine residue was used to prepare a compound with a drug\u2013antibody ratio of 2 and favorable biophysical properties. The antibody was rapidly taken up by the target cells, showing almost complete internalization after 4 h of treatment. Its cytotoxic effect was potentiated upon cross-linking mediated by an anti-human IgG F(ab\u2019)2 fragment. Because of its fast internalization and strict target specificity, this antibody\u2013drug conjugate presents a valuable starting point for the further development of an anti-IgE cell-depleting agent, operating by the combined action of receptor cross-linking and toxin-mediated cytotoxicity.<\/jats:p>","DOI":"10.3390\/ijms241914997","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T04:56:43Z","timestamp":1696827403000},"page":"14997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of a Cytotoxic Antibody\u2013Drug Conjugate Targeting Membrane Immunoglobulin E-Positive Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Aleksandra","family":"Rodak","sequence":"first","affiliation":[{"name":"Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-5874","authenticated-orcid":false,"given":"Katharina","family":"Stadlbauer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhusudhan Reddy","family":"Bobbili","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria"},{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstra\u00dfe 13, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oskar","family":"Smrzka","sequence":"additional","affiliation":[{"name":"Ablevia Biotech GmbH, Maria Jacobi Gasse 1, 1030 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-2686","authenticated-orcid":false,"given":"Florian","family":"R\u00fcker","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-070X","authenticated-orcid":false,"given":"Gordana","family":"Wozniak Knopp","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/35037000","article-title":"The epidemic of allergy and asthma","volume":"402","author":"Holgate","year":"1999","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nri2273","article-title":"IgE in allergy and asthma today","volume":"8","author":"Gould","year":"2008","journal-title":"Nat. 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