{"entity": "researcher", "timestamp": "2026-08-22T08:30:45.038Z", "family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "affiliations": ["Department of Protein Science, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146"}}, "publications": [{"entity": "publication", "iuid": "fe07ae0a7fad420aad6593affa247d96", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fe07ae0a7fad420aad6593affa247d96.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fe07ae0a7fad420aad6593affa247d96"}}, "title": "Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model.", "authors": [{"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}}, {"family": "Tashireva", "given": "Liubov A", "initials": "LA", "orcid": "0000-0003-2061-8417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e462c38bfd8846588156097b5602341a.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Deyev", "given": "Sergey M", "initials": "SM", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.json"}}], "type": "journal article", "published": "2021-08-04", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "16", "issn-l": "2072-6694"}, "abstract": "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.", "doi": "10.3390/cancers13163939", "pmid": "34439094", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8393281"}, {"db": "pii", "key": "cancers13163939"}], "notes": [], "created": "2026-08-21T13:01:44.880Z", "modified": "2026-08-21T13:01:45.042Z"}, {"entity": "publication", "iuid": "f34c53feced64382a61689e6e503325f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f34c53feced64382a61689e6e503325f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f34c53feced64382a61689e6e503325f"}}, "title": "Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1.", "authors": [{"family": "Deyev", "given": "Sergey M", "initials": "SM", "orcid": "0000-0002-3952-0631", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb88df2aaa8a46a5957370b9258e2834.json"}}, {"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Liu", "given": "Yongsheng", "initials": "Y", "orcid": "0000-0001-5871-5779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a53363bbcb5b414681ee46ac22b65230.json"}}, {"family": "Schulga", "given": "Alexey", "initials": "A", "orcid": "0000-0003-3425-0828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45b1c8e5447c41bbb93e61706377a0c7.json"}}, {"family": "Konovalova", "given": "Elena", "initials": "E"}, {"family": "Garousi", "given": "Javad", "initials": "J"}, {"family": "Rinne", "given": "Sara S", "initials": "SS", "orcid": "0000-0003-2141-3982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3aea3edd98b441c98bb527b1e0c911f5.json"}}, {"family": "Larkina", "given": "Maria", "initials": "M", "orcid": "0000-0003-1176-2441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/557c8a9c8b2142a7a88d6211335d24e4.json"}}, {"family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}], "type": "journal article", "published": "2021-07-17", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "14", "issn-l": "2072-6694"}, "abstract": "The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [125I]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.", "doi": "10.3390/cancers13143589", "pmid": "34298801", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8304184"}, {"db": "pii", "key": "cancers13143589"}], "notes": [], "created": "2026-08-21T13:01:42.532Z", "modified": "2026-08-21T13:01:42.881Z"}, {"entity": "publication", "iuid": "1c45026f03674ba1bf2b988dd07f1f1e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1c45026f03674ba1bf2b988dd07f1f1e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1c45026f03674ba1bf2b988dd07f1f1e"}}, "title": "Incorporation of a Hydrophilic Spacer Reduces Hepatic Uptake of HER2-Targeting Affibody-DM1 Drug Conjugates.", "authors": [{"family": "Ding", "given": "Haozhong", "initials": "H", "orcid": "0000-0003-1093-8222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ee6fb5a9b694c1d8a40cc41e9d16146.json"}}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2019-08-14", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "11", "issue": "8", "issn-l": "2072-6694"}, "abstract": "Affibody molecules are small affinity-engineered scaffold proteins which can be engineered to bind to desired targets. The therapeutic potential of using an affibody molecule targeting HER2, fused to an albumin-binding domain (ABD) and conjugated with the cytotoxic maytansine derivate MC-DM1 (AffiDC), has been validated. Biodistribution studies in mice revealed an elevated hepatic uptake of the AffiDC, but histopathological examination of livers showed no major signs of toxicity. However, previous clinical experience with antibody drug conjugates have revealed a moderate- to high-grade hepatotoxicity in treated patients, which merits efforts to also minimize hepatic uptake of the AffiDCs. In this study, the aim was to reduce the hepatic uptake of AffiDCs and optimize their in vivo targeting properties. We have investigated if incorporation of hydrophilic glutamate-based spacers adjacent to MC-DM1 in the AffiDC, (ZHER2:2891)2-ABD-MC-DM1, would counteract the hydrophobic nature of MC-DM1 and, hence, reduce hepatic uptake. Two new AffiDCs including either a triglutamate-spacer-, (ZHER2:2891)2-ABD-E3-MC-DM1, or a hexaglutamate-spacer-, (ZHER2:2891)2-ABD-E6-MC-DM1 next to the site of MC-DM1 conjugation were designed. We radiolabeled the hydrophilized AffiDCs and compared them, both in vitro and in vivo, with the previously investigated (ZHER2:2891)2-ABD-MC-DM1 drug conjugate containing no glutamate spacer. All three AffiDCs demonstrated specific binding to HER2 and comparable in vitro cytotoxicity. A comparative biodistribution study of the three radiolabeled AffiDCs showed that the addition of glutamates reduced drug accumulation in the liver while preserving the tumor uptake. These results confirmed the relation between DM1 hydrophobicity and liver accumulation. We believe that the drug development approach described here may also be useful for other affinity protein-based drug conjugates to further improve their in vivo properties and facilitate their clinical translatability.", "doi": "10.3390/cancers11081168", "pmid": "31416167", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6721809"}, {"db": "pii", "key": "cancers11081168"}], "notes": [], "created": "2026-08-21T13:01:27.719Z", "modified": "2026-08-21T13:01:27.833Z"}]}