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Preclinical Evaluat...
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Deyev, Sergey M.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, Russia,Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
(författare)
Preclinical Evaluation of HER2-Targeting DARPin G3: Impact of Albumin-Binding Domain (ABD) Fusion
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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Multidisciplinary Digital Publishing Institute (MDPI),2024
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-346391
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-346391URI
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https://doi.org/10.3390/ijms25084246DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-528214URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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QC 20240516
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The two first authors contributed equally.Corresponding author: Vladimir Tolmachev
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Oroujeni, Maryam,PhD,1982-Uppsala universitet,Cancerprecisionsmedicin,Affibody AB, S-17165 Solna, Sweden.(Swepub:uu)maror883
(författare)
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Garousi, JavadUppsala universitet,KTH,Proteinvetenskap,Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden,Cancerprecisionsmedicin,KTH Royal Inst Technol, Dept Prot Sci, S-10691 Stockholm, Sweden.(Swepub:uu)javga723
(författare)
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Gräslund, Torbjörn,1970-KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, S-10691 Stockholm, Sweden.(Swepub:kth)u1dl39rj
(författare)
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Li, RuonanKTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, S-10691 Stockholm, Sweden.(Swepub:kth)u1zfqnss
(författare)
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Rosly, Alia Hani BintiUppsala universitet,Cancerprecisionsmedicin
(författare)
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Orlova, Anna,1960-Uppsala universitet,Theranostics(Swepub:uu)annaorlo
(författare)
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Konovalova, ElenaMolecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia,Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.
(författare)
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Schulga, AlexeyMolecular 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, Russia,Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
(författare)
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Vorobyeva, AnzhelikaUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)anzvo555
(författare)
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Tolmachev, VladimirUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)vladtolm
(författare)
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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, RussiaRussian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:International Journal of Molecular Sciences: Multidisciplinary Digital Publishing Institute (MDPI)25:81661-65961422-0067
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Deyev, Sergey M.
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Oroujeni, Maryam ...
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Garousi, Javad
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Gräslund, Torbjö ...
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Li, Ruonan
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Rosly, Alia Hani ...
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Orlova, Anna, 19 ...
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Konovalova, Elen ...
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Schulga, Alexey
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Vorobyeva, Anzhe ...
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Tolmachev, Vladi ...
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