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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 (författare)

Preclinical Evaluation of HER2-Targeting DARPin G3: Impact of Albumin-Binding Domain (ABD) Fusion

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • Multidisciplinary Digital Publishing Institute (MDPI),2024
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-346391
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-346391URI
  • https://doi.org/10.3390/ijms25084246DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20240516
  • 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 ...)

  • Oroujeni, MaryamDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;; Affibody AB, 171 65 Solna, Sweden (författare)
  • Garousi, JavadKTH,Proteinvetenskap,Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden(Swepub:kth)u109843g (författare)
  • Gräslund, Torbjörn,1970-KTH,Proteinvetenskap(Swepub:kth)u1dl39rj (författare)
  • Li, RuonanKTH,Proteinvetenskap(Swepub:kth)u1zfqnss (författare)
  • Rosly, Alia Hani BintiDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden; (författare)
  • Orlova, AnnaDepartment of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden; (författare)
  • Konovalova, ElenaMolecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia (författare)
  • 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 (författare)
  • Vorobyeva, AnzhelikaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden; (författare)
  • Tolmachev, VladimirDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden; (författare)
  • 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, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;; Affibody AB, 171 65 Solna, Sweden (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:International Journal of Molecular Sciences: Multidisciplinary Digital Publishing Institute (MDPI)25:81661-65961422-0067

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