{"entity": "publication", "iuid": "5f65ced79c3b40ea96ee5e9e78ca4d73", "timestamp": "2026-08-22T06:56:32.634Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5f65ced79c3b40ea96ee5e9e78ca4d73.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5f65ced79c3b40ea96ee5e9e78ca4d73"}}, "title": "Targeting Tumor Cells Overexpressing the Human Epidermal Growth Factor Receptor 3 with Potent Drug Conjugates Based on Affibody Molecules.", "authors": [{"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Yin", "given": "Wen", "initials": "W"}, {"family": "Borras", "given": "Anna Mestre", "initials": "AM"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}}], "type": "journal article", "published": "2022-05-31", "journal": {"title": "Biomedicines", "issn": "2227-9059", "volume": "10", "issue": "6", "issn-l": null}, "abstract": "Increasing evidence suggests that therapy targeting the human epidermal growth factor receptor 3 (HER3) could be a viable route for targeted cancer therapy. Here, we studied a novel drug conjugate, ZHER3-ABD-mcDM1, consisting of a HER3-targeting affibody molecule, coupled to the cytotoxic tubulin polymerization inhibitor DM1, and an albumin-binding domain for in vivo half-life extension. ZHER3-ABD-mcDM1 showed a strong affinity to the extracellular domain of HER3 (KD 6 nM), and an even stronger affinity (KD 0.2 nM) to the HER3-overexpressing pancreatic carcinoma cell line, BxPC-3. The drug conjugate showed a potent cytotoxic effect on BxPC-3 cells with an IC50 value of 7 nM. Evaluation of a radiolabeled version, [99mTc]Tc-ZHER3-ABD-mcDM1, showed a relatively high rate of internalization, with a 27% internalized fraction after 8 h. Further in vivo evaluation showed that it could target BxPC-3 (pancreatic carcinoma) and DU145 (prostate carcinoma) xenografts in mice, with an uptake peaking at 6.3 \u00b1 0.4% IA/g at 6 h post-injection for the BxPC-3 xenografts. The general biodistribution showed uptake in the liver, lung, salivary gland, stomach, and small intestine, organs known to express murine ErbB3 naturally. The results from the study show that ZHER3-ABD-mcDM1 is a highly potent and selective drug conjugate with the ability to specifically target HER3 overexpressing cells. Further pre-clinical and clinical development is discussed.", "doi": "10.3390/biomedicines10061293", "pmid": "35740315", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9219639"}, {"db": "pii", "key": "biomedicines10061293"}], "notes": [], "created": "2026-08-21T13:01:13.994Z", "modified": "2026-08-21T13:01:14.186Z"}