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Sökning: onr:"swepub:oai:DiVA.org:kth-346391" > Preclinical Evaluat...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005127naa a2200493 4500
001oai:DiVA.org:kth-346391
003SwePub
008240514s2024 | |||||||||||000 ||eng|
024a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3463912 URI
024a https://doi.org/10.3390/ijms250842462 DOI
040 a (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Deyev, Sergey M.u Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia4 aut
2451 0a Preclinical Evaluation of HER2-Targeting DARPin G3: Impact of Albumin-Binding Domain (ABD) Fusion
264 1b Multidisciplinary Digital Publishing Institute (MDPI),c 2024
338 a print2 rdacarrier
500 a QC 20240516
520 a Designed ankyrin repeat protein (DARPin) G3 is an engineered scaffold protein. This small (14.5 kDa) targeting protein binds with high affinity to human epidermal growth factor receptor 2 (HER2). HER2 is overexpressed in several cancers. The use of the DARPin G3 for radionuclide therapy is complicated by its high renal reabsorption after clearance via the glomeruli. We tested the hypothesis that a fusion of the DARPin G3 with an albumin-binding domain (ABD) would prevent rapid renal excretion and high renal reabsorption resulting in better tumour targeting. Two fusion proteins were produced, one with the ABD at the C-terminus (G3-ABD) and another at the N-terminus (ABD-G3). Both variants were labelled with 177Lu. The binding properties of the novel constructs were evaluated in vitro and their biodistribution was compared in mice with implanted human HER2-expressing tumours. Fusion with the ABD increased the retention time of both constructs in blood compared with the non-ABD-fused control. The effect of fusion with the ABD depended strongly on the order of the domains in the constructs, resulting in appreciably better targeting properties of [177Lu]Lu-G3-ABD. Our data suggest that the order of domains is critical for the design of targeting constructs based on scaffold proteins.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Radiologi och bildbehandling0 (SwePub)302082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Radiology, Nuclear Medicine and Medical Imaging0 (SwePub)302082 hsv//eng
653 a albumin-binding domain (ABD)
653 a DARPin G3
653 a HER2
653 a Lutetium-177 ( Lu) 177
653 a SKOV-3 xenograft
653 a SPECT imaging
700a Oroujeni, Maryamu Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;; Affibody AB, 171 65 Solna, Sweden4 aut
700a Garousi, Javadu KTH,Proteinvetenskap,Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden4 aut0 (Swepub:kth)u109843g
700a Gräslund, Torbjörn,d 1970-u KTH,Proteinvetenskap4 aut0 (Swepub:kth)u1dl39rj
700a Li, Ruonanu KTH,Proteinvetenskap4 aut0 (Swepub:kth)u1zfqnss
700a Rosly, Alia Hani Bintiu Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;4 aut
700a Orlova, Annau Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden;4 aut
700a Konovalova, Elenau Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia4 aut
700a Schulga, Alexeyu Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia4 aut
700a Vorobyeva, Anzhelikau Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;4 aut
700a Tolmachev, Vladimiru Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;4 aut
710a Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russiab Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;; Affibody AB, 171 65 Solna, Sweden4 org
773t International Journal of Molecular Sciencesd : Multidisciplinary Digital Publishing Institute (MDPI)g 25:8q 25:8x 1661-6596x 1422-0067
856u https://doi.org/10.3390/ijms25084246y Fulltext
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-346391
8564 8u https://doi.org/10.3390/ijms25084246

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