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Biologic Evaluation...
Biologic Evaluation of a Heterodimeric HER2-Albumin Targeted Affibody Molecule Produced by Chemo-Enzymatic Peptide Synthesis
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- Liu, Yongsheng (författare)
- Uppsala universitet,Cancerprecisionsmedicin
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- Gueler, Rezan (författare)
- Affibody AB, S-17165 Solna, Sweden.
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- Liao, Yunqi (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Cancerprecisionsmedicin
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- Widmark, Olof (författare)
- Affibody AB, S-17165 Solna, Sweden.
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- Meuleman, Theodorus J. J. (författare)
- EnzyTag BV, Daelderweg 9, NL-6361 HK Nuth, Netherlands.
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- Koijen, Anna (författare)
- EnzyTag BV, Daelderweg 9, NL-6361 HK Nuth, Netherlands.
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- van den Bos, Leendert J. J. (författare)
- EnzyTag BV, Daelderweg 9, NL-6361 HK Nuth, Netherlands.
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- Naasz, Robert (författare)
- EnzyTag BV, Daelderweg 9, NL-6361 HK Nuth, Netherlands.
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- Bodenko, Vitalina (författare)
- Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
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- Ekblad, Caroline (författare)
- Affibody AB, S-17165 Solna, Sweden.
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
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- Frejd, Fredrik Y. (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Affibody AB, S-17165 Solna, Sweden.
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(creator_code:org_t)
- 2022-11-19
- 2022
- Engelska.
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923 .- 1999-4923. ; 14:11
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Targeted molecular radiation therapy is a promising emerging treatment modality in oncology, and peptide synthesis may shorten the time to reach the clinical stage. In this study, we have explored Chemo-Enzymatic Peptide Synthesis, or CEPS, as a new means of producing a therapeutic HER2 targeted Affibody((R)) molecule, comprising a C-terminal albumin binding domain (ABD) for half-life extension and a total length of 108 amino acids. In addition, a DOTA moiety could be incorporated at N-terminus directly during the synthesis step and subsequently utilized for site-specific radiolabeling with the therapeutic radionuclide Lu-177. Retained thermodynamic stability as well as retained binding to both HER2 and albumin was verified. Furthermore, HER2 binding specificity of the radiolabeled Affibody molecule was confirmed by an in vitro saturation assay showing a significantly higher cell-bound activity of SKOV-3 (high HER2 expression) compared with BxPC3 (low HER2 expression), both in the presence and absence of HSA. In vivo evaluation in mice bearing HER2 expressing xenografts also showed specific tumor targeting as well as extended time in circulation and reduced kidney uptake compared with a HER2 targeted Affibody molecule without the ABD moiety. To conclude, we have demonstrated that CEPS can be used for production of Affibody-fusion molecules with retained in vitro and in vivo functionality.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Affibody molecule
- albumin binding domain (ABD)
- peptide synthesis
- enzymatic ligation
- scaffold protein
- radionuclide therapy
- Lu-177
- DOTA
- SKOV-3 xenograft
- biodistribution
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Liu, Yongsheng
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Gueler, Rezan
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Liao, Yunqi
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Vorobyeva, Anzhe ...
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Widmark, Olof
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Meuleman, Theodo ...
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Koijen, Anna
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van den Bos, Lee ...
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Naasz, Robert
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Bodenko, Vitalin ...
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Orlova, Anna, 19 ...
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Ekblad, Caroline
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Tolmachev, Vladi ...
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Frejd, Fredrik Y ...
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- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
- Artiklar i publikationen
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Pharmaceutics
- Av lärosätet
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Uppsala universitet