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Half-life extension via ABD-fusion leads to higher tumor uptake of an affibody-drug conjugate compared to PAS- and XTENylation.

Zhang, Jie (författare)
KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden.
Bodenko, Vitalina (författare)
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia, Tomsk Polytechnic University; Scientific and Educational Laboratory of Chemical and Pharmaceutical Research, Siberian State Medical University, Ministry of Health of the Russian Federation, 634050 Tomsk, Russia,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Siberian State Med Univ, Sci & Educ Lab Chem & Pharmaceut Res, Minist Hlth Russian Federat, Tomsk 634050, Russia.
Larkina, Maria (författare)
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia, Tomsk Polytechnic University; Siberian State Medical University, Ministry of Health of the Russian Federation, 634050 Tomsk, Russia; National Research Tomsk Polytechnic University, 634050 Tomsk, Russia,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Siberian State Med Univ, Minist Hlth Russian Federat, Tomsk 634050, Russia.
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Bezverkhniaia, Ekaterina (författare)
Uppsala universitet,Theranostics,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
Xu, Tianqi (författare)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Liao, Yunqi (författare)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Abouzayed, Ayman (författare)
Uppsala universitet,Theranostics,Translationell avbildning med PET
Plotnikov, Evgenii (författare)
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia, Tomsk Polytechnic University,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
Tretyakova, Maria (författare)
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia, Tomsk Polytechnic University,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
Yuldasheva, Feruza (författare)
Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia, Tomsk Polytechnic University,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
Belousov, Mikhail V. (författare)
Uppsala universitet,Institutionen för läkemedelskemi,Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.
Orlova, Anna, 1960- (författare)
Uppsala universitet,Theranostics,Cancerprecisionsmedicin
Tolmachev, Vladimir (författare)
Uppsala universitet,Cancerprecisionsmedicin
Gräslund, Torbjörn, 1970- (författare)
KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Roslagstullsbacken 21, S-11417 Stockholm, Sweden.
Vorobyeva, Anzhelika (författare)
Uppsala universitet,Cancerprecisionsmedicin
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 (creator_code:org_t)
Elsevier BV, 2024
2024
Engelska.
Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 370, s. 468-478
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • A critical parameter during the development of protein therapeutics is to endow them with suitable pharmacokinetic and pharmacodynamic properties. Small protein drugs are quickly eliminated by kidney filtration, and in vivo half-life extension is therefore often desired. Here, different half-life extension technologies were studied where PAS polypeptides (PAS300, PAS600), XTEN polypeptides (XTEN288, XTEN576), and an albumin binding domain (ABD) were compared for half-life extension of an anti-human epidermal growth factor receptor 2 (HER2) affibody-drug conjugate. The results showed that extension with the PAS or XTEN polypeptides or the addition of the ABD lowered the affinity for HER2 to some extent but did not negatively affect the cytotoxic potential. The half-lives in mice ranged from 7.3 h for the construct including PAS300 to 11.6 h for the construct including PAS600. The highest absolute tumor uptake was found for the construct including the ABD, which was 60 to 160% higher than the PASylated or XTENylated constructs, even though it did not have the longest half-life (9.0 h). A comparison of the tumor-to-normal-organ ratios showed the best overall performance of the ABD-fused construct. In conclusion, PASylation, XTENylation, and the addition of an ABD are viable strategies for half-life extension of affibody-drug conjugates, with the best performance observed for the construct including the ABD.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

ABD
Affibody molecule
Affibody-drug conjugate
Albumin binding domain
DM1
Half-life
HER2
PASylation
XTENylation

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art (ämneskategori)

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