{"entity": "researcher", "timestamp": "2026-10-07T23:43:17.970Z", "family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "affiliations": ["Department of Medicinal Chemistry, Uppsala University, Uppsala751 23, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/429656452a7b4a13a034a31d84a1c518.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/429656452a7b4a13a034a31d84a1c518"}}, "publications": [{"entity": "publication", "iuid": "3184e0c603834b1cbee2725ab7a1e566", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3184e0c603834b1cbee2725ab7a1e566.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3184e0c603834b1cbee2725ab7a1e566"}}, "title": "Integrating Tumor Targeting and Half-Life Extension into a Dual-Surfaced Single-Domain ADAPT Protein.", "authors": [{"family": "Larsson", "given": "Emma", "initials": "E"}, {"family": "Ud-Din", "given": "Moeen", "initials": "M"}, {"family": "Bitzios", "given": "Athanasios", "initials": "A"}, {"family": "Recasens P\u00e9rez-Vera", "given": "Enrique", "initials": "E"}, {"family": "Tegel", "given": "Hanna", "initials": "H", "orcid": "0000-0002-7067-9173", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d733dbd7b84a6b88f7f5fcff7165f6.json"}}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications.scilifelab.se/researcher/429656452a7b4a13a034a31d84a1c518.json"}}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e8511ebb1e74f1c9149f11951149793.json"}}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A", "orcid": "0000-0002-4778-3909", "researcher": {"href": "https://publications.scilifelab.se/researcher/e27128cb208143edae63b7730ba0de88.json"}}, {"family": "Hober", "given": "Sophia", "initials": "S", "orcid": "0000-0003-0605-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8dd8ee4264d4e4b912dacad3106f40a.json"}}], "type": "journal article", "published": "2026-09-07", "journal": {"title": "Mol. Pharm.", "issn": "1543-8392", "volume": "23", "issue": "9", "pages": "4743-4757", "issn-l": "1543-8384"}, "abstract": "Folate receptor alpha (FR\u03b1) is frequently overexpressed in ovarian cancer while showing limited expression in healthy tissues. Targeting of FR\u03b1 has been extensively investigated using antibody-based therapies but less so with small scaffold proteins. Small scaffold proteins represent an alternative approach with potential advantages such as site-specific conjugation and deep tumor penetration but are limited by a short half-life. Here, we describe the development of a dual-surfaced ADAPT scaffold protein (6 kDa) with simultaneous bispecificity for FR\u03b1 and albumin. Using combinatorial libraries and phage display, we identified a candidate, termed ADAPT22, with high isoform selectivity and subnanomolar affinity for FR\u03b1 (KD = 0.8 nM), paired with a low nanomolar affinity for albumin (KD = 2.4 nM). Importantly, ADAPT22 is able to interact with both targets simultaneously, truly combining extended retention in blood via albumin association and tumor targeting via FR\u03b1 within a single-domain protein. The simultaneous nature was verified in vitro to soluble proteins and to FR\u03b1-positive cells and in vivo using a mouse xenograft model. In mice, ADAPT22 demonstrated markedly extended blood retention, reduced renal uptake, and specific accumulation in FR\u03b1-positive tumors, confirming simultaneous dual-surface binding. To the best of our knowledge, this is the smallest half-life extended affinity protein designed for therapeutic targeting of FR\u03b1.", "doi": "10.1021/acs.molpharmaceut.6c00683", "pmid": "42704121", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13556137"}, {"db": "pii", "key": "5236189"}], "notes": [], "created": "2026-10-07T13:57:08.917Z", "modified": "2026-10-07T13:57:09.427Z"}]}