{"entity": "researcher", "timestamp": "2026-08-22T06:59:12.152Z", "family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "affiliations": ["Department of Protein Science, KTH Royal Institute of Technology, 114 17 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/afff2431691348539334ab0e86158505"}}, "publications": [{"entity": "publication", "iuid": "5f65ced79c3b40ea96ee5e9e78ca4d73", "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"}, {"entity": "publication", "iuid": "658dcf32f8274f2caf86feccdd64ae49", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/658dcf32f8274f2caf86feccdd64ae49.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/658dcf32f8274f2caf86feccdd64ae49"}}, "title": "The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy.", "authors": [{"family": "Yin", "given": "Wen", "initials": "W"}, {"family": "Xu", "given": "Tianqi", "initials": "T", "orcid": "0000-0002-1826-4093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/688f685bf3474e72bfab58e1fa2035b9.json"}}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Oroujeni", "given": "Maryam", "initials": "M", "orcid": "0000-0003-2660-9837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bdd7a76401c42b4bbe8b11cfdb83212.json"}}, {"family": "Zhang", "given": "Jie", "initials": "J", "orcid": "0000-0002-4472-3468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b392e01b09d47e28f284d6f45e5bd93.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99703faa11ab4c19aff2f426f61c3134.json"}}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Vtorushin", "given": "Sergey V", "initials": "SV"}, {"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", "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"}}], "type": "journal article", "published": "2021-11-21", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "13", "issue": "11", "issn-l": null}, "abstract": "Human epidermal growth factor receptor 2 (HER2) is a clinically validated target for breast cancer therapy. Previously, a drug-fused HER2-targeting affinity protein construct successfully extended the survival of mice bearing HER2-expressing xenografts. The aim of this study was to evaluate the influence of the number and positioning of the protein domains in the drug conjugate. Seven HER2-targeting affibody-based constructs, including one or two affibody molecules (Z) with or without an albumin-binding domain (ABD), namely Z, Z-ABD, ABD-Z, Z-Z, Z-Z-ABD, Z-ABD-Z, and ABD-Z-Z, were evaluated on their effects on cell growth, in vivo targeting, and biodistribution. The biodistribution study demonstrated that the monomeric constructs had longer blood retention and lower hepatic uptake than the dimeric ones. A dimeric construct, specifically ABD-Z-Z, could stimulate the proliferation of HER2 expressing SKOV-3 cells in vitro and the growth of tumors in vivo, whereas the monomeric construct Z-ABD could not. These two constructs demonstrated a therapeutic effect when coupled to mcDM1; however, the effect was more pronounced for the non-stimulating Z-ABD. The median survival of the mice treated with Z-ABD-mcDM1 was 63 days compared to the 37 days for those treated with ABD-Z-Z-mcDM1 or for the control animals. Domain permutation of an ABD-fused HER2-targeting affibody-based drug conjugate significantly influences tumor cell proliferation and therapy efficacy. The monomeric conjugate Z-ABD is the most promising format for targeted delivery of the cytotoxic drug DM1.", "doi": "10.3390/pharmaceutics13111974", "pmid": "34834389", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8617914"}, {"db": "pii", "key": "pharmaceutics13111974"}], "notes": [], "created": "2026-08-21T13:04:54.714Z", "modified": "2026-08-21T13:04:54.844Z"}, {"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"}]}