{"entity": "researcher", "timestamp": "2026-10-18T01:07:00.066Z", "family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "affiliations": ["Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, SE-751 83, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/b32c5baa141647359f57f4bc9f63dbe9.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/b32c5baa141647359f57f4bc9f63dbe9"}}, "publications": [{"entity": "publication", "iuid": "5aa8ec8ea5b1403da8e87029b19a2c1d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5aa8ec8ea5b1403da8e87029b19a2c1d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5aa8ec8ea5b1403da8e87029b19a2c1d"}}, "title": "Combining bacterial display and protein language models to engineer a CD69-binding affibody for molecular imaging of immune activation.", "authors": [{"family": "Olsson", "given": "Hugo", "initials": "H"}, {"family": "Westerberg", "given": "Cornelia", "initials": "C", "orcid": "0009-0005-0274-063X", "researcher": {"href": "https://publications.scilifelab.se/researcher/118fa47f8d44438788c2189691857f36.json"}}, {"family": "Persson", "given": "Jonas", "initials": "J"}, {"family": "L\u00f6fstrand", "given": "Lina", "initials": "L"}, {"family": "Korsgren", "given": "Olle", "initials": "O", "orcid": "0000-0002-8524-9547", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b60c2f86ae7428c9c0001681103c187.json"}}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications.scilifelab.se/researcher/b32c5baa141647359f57f4bc9f63dbe9.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications.scilifelab.se/researcher/619dac079e47478d859f562aea39e49b.json"}}], "type": "journal article", "published": "2026-01-09", "journal": {"title": "Protein Eng. Des. Sel.", "issn": "1741-0134", "volume": "39", "issn-l": "1741-0126"}, "abstract": "Recent years have seen remarkable clinical success with therapies that harness the patient's immune system, with checkpoint inhibitors in oncology as a prominent example. Non-invasive monitoring of immune activation in vivo has the potential to accelerate both basic immunology research and clinical drug development, offering a valuable means to track responses to emerging immunotherapies. CD69 is a rapidly induced activation marker on lymphocytes and other leukocytes, making it an attractive imaging target. For such applications, affibody molecules offer distinct advantages as radio imaging tracers due to their small size, high affinity, and rapid pharmacokinetics, resulting in excellent imaging contrast. Here, we combined directed evolution with computational design to optimise a CD69-binding affibody molecule. An alanine scan of the parental binder informed the construction of a diversification library, which was displayed on Escherichia coli and subjected to iterative MACS and FACS selections with stringent off-rate competition. The top selection hit was subsequently refined through site-directed mutagenesis, including variants suggested by a general protein language model. The resulting lead, Z1525, bound human CD69 with single-digit nanomolar affinity and showed improved thermal stability while retaining solubility and refolding capacity, consistent with suitability for radiolabelling and in vivo targeting. Most importantly, it displayed selective binding to CD69 on stimulated Jurkat cells, with negligible binding to resting cells. These results establish E. coli display with off-rate-driven selection as an efficient strategy for affibody affinity maturation and demonstrate that protein language models can effectively guide improvements in folding stability. Z1525 represents a promising radio imaging tracer candidate for monitoring immune activation in vivo and warrants further preclinical development.", "doi": "10.1093/protein/gzag013", "pmid": "42275072", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13284772"}, {"db": "pii", "key": "8706316"}], "notes": [], "created": "2026-10-14T12:54:35.460Z", "modified": "2026-10-14T12:54:35.665Z"}, {"entity": "publication", "iuid": "f502890aac5f4eb28a801d8113afa0e0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f502890aac5f4eb28a801d8113afa0e0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f502890aac5f4eb28a801d8113afa0e0"}}, "title": "PDGFR\u00df targeted positron emission tomography as a non-invasive biomarker for activated hepatic stellate cells: lasts steps before clinical translation.", "authors": [{"family": "Yashaswini", "given": "Chittampalli N", "initials": "CN"}, {"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Papadopoulos", "given": "Natalia", "initials": "N"}, {"family": "Wegrzyniak", "given": "Olivia", "initials": "O"}, {"family": "L\u00f6fblom", "given": "John", "initials": "J"}, {"family": "Nordstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Velikyan", "given": "Irina", "initials": "I"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Hagmar", "given": "Per", "initials": "P"}, {"family": "Wagner", "given": "Michael", "initials": "M"}, {"family": "Frejd", "given": "Fredrik Y", "initials": "FY"}, {"family": "Korsgren", "given": "Olle", "initials": "O"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Friedman", "given": "Scott L", "initials": "SL"}, {"family": "Eriksson", "given": "Olof", "initials": "O", "orcid": "0000-0002-2515-8790", "researcher": {"href": "https://publications.scilifelab.se/researcher/b32c5baa141647359f57f4bc9f63dbe9.json"}}], "type": "journal article", "published": "2025-12-13", "journal": {"title": "EJNMMI Radiopharm Chem", "issn": "2365-421X", "volume": "10", "issue": "1", "pages": "80", "issn-l": null}, "abstract": "BACKGROUND: Activated hepatic stellate cells (aHSCs) are the key cell population in the injured liver driving fibrogenesis. aHSCs express platelet-derived growth factor receptor beta (PDGFR\u00df), which is absent from quiescent HSCs. PDGFR\u00df is therefore an attractive target of PET tracers for imaging of fibrogenesis. Here, we present the pharmacological characterization of [68Ga]Ga-DOTA-Cys-ATH001 in preparation for clinical translation and further confirm PDGFR\u00df as a biomarker of activated HSCs in liver disease by single cell sequencing. METHODS: The expression of PDGFR\u00df in subpopulations of HSCs was evaluated in scRNAseq datasets from both a mouse and human liver samples. DOTA-Cys-ATH001 was evaluated for affinity and mechanism of binding to PDGFR\u00df. [68Ga]Ga-DOTA-Cys-ATH001 was evaluated for binding in vitro in mouse and human liver biopsies. The in vivo stability, biodistribution, pharmacokinetics, dosimetry and microdosing toxicology were evaluated in rats and pigs. RESULTS: PDGFR\u00df expression was specifically upregulated in activated HSCs. [68Ga]Ga-DOTA-Cys-ATH001 could differentiate fibrotic liver from healthy liver. The binding co-localized with tissue areas positive for collagen deposition and PDGFR\u00df immunostaining. Based on the microdosing toxicology study the no observed adverse effect level was at least 1000 \u00b5g/kg, suggesting that the intended clinical PET scan dose is safe for use. Dosimetry calculations of [68Ga]Ga-DOTA-Cys-ATH001 predicted an effective dose in human amenable to repeated examinations. CONCLUSIONS: The data presented here suggests that PDGFR\u03b2 PET imaging with [68Ga]Ga-DOTA-Cys-ATH001 has potential for non-invasive detection of activated HSCs. Clinical translation of [68Ga]Ga-DOTA-Cys-ATH001 is ongoing.", "doi": "10.1186/s41181-025-00410-2", "pmid": "41389114", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12711615"}, {"db": "pii", "key": "10.1186/s41181-025-00410-2"}], "notes": [], "created": "2026-10-16T15:34:04.820Z", "modified": "2026-10-16T15:34:04.832Z"}]}