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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003230nam a2200529 4500
001oai:DiVA.org:kth-334734
003SwePub
008230824| | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3347342 URI
040 a (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a vet2 swepub-contenttype
072 7a ovr2 swepub-publicationtype
1001 a Zhang, Jieu KTH,Proteinvetenskap4 aut0 (Swepub:kth)u1h5ixom
2451 0a A Comparison of in vivo Half-life Extension of Affibody-Drug Conjugates by PASylation, XTENylation and Albumin Binding
338 a print2 rdacarrier
500 a QC 20230824
520 a Drug conjugates based on engineered scaffold affinity proteins hold promise to become potent targeted cancer drugs in the future, and an important aspect is to provide them with optimal pharmacokinetic properties. In this study, we investigated different half-life extension technologies for HER2-specific affibody-drug conjugates (AffiDCs), and the effect they imposed on the uptake in tumors and normal organs and tissues. Two sizes of unstructured PAS and XTEN polypeptides (PAS300, PAS600, XTEN288, and XTEN576) and an albumin binding domain (ABD) were used for the comparison. The results showed that extension with the PAS or XTEN polypeptides as well as the addition of the ABD did not affect HER2 binding or the cytotoxic potential negatively. There was a difference in half-lives in mice, which ranged from 7.3 h for the construct including PAS300 to 11.6 h for the construct including the PAS600 polypeptide. The highest absolute tumor uptake was found for the construct including the ABD, even though it did not have the longest in vivo half-life (9.0 h). Consequently, the construct with the ABD gave the highest tumor-to-normal-organ ratios. In conclusion, PASylation, XTENylation, and the addition of an ABD appear to be viable strategies for half-life extension of affibody drug conjugates, with the best in vivo performance observed for the construct including the ABD. 
650 7a TEKNIK OCH TEKNOLOGIERx Industriell bioteknikx Läkemedelsbioteknik0 (SwePub)209052 hsv//swe
650 7a ENGINEERING AND TECHNOLOGYx Industrial Biotechnologyx Pharmaceutical Biotechnology0 (SwePub)209052 hsv//eng
653 a Affibody molecule
653 a HER2
653 a PASylation
653 a XTENylation
653 a DM1
653 a affibody-drug conjugate
653 a half-life
653 a biodistribution
653 a Biotechnology
653 a Bioteknologi
7001 a Bodenko, Vitalina4 aut
7001 a Larkina, Maria4 aut
7001 a Bezverkhnyaya, Yekaterina4 aut
7001 a Xu, Tianqi4 aut
7001 a Liao, Yunqi4 aut
7001 a Abouzayed, Ayman4 aut
7001 a Plotnikov, Evgenij4 aut
7001 a Maria, Tretyakova4 aut
7001 a Yuldasheva, Feruza4 aut
7001 a Belousov, Mikhail V4 aut
7001 a Orlova, Anna4 aut
7001 a Tolmachev, Vladimir4 aut
7001 a Gräslund, Torbjörn4 aut
7001 a Vorobyeva, Anzhelika4 aut
7102 a KTHb Proteinvetenskap4 org
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-334734

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