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Engineering of a bispecific affibody molecule towards HER2 and HER3 by addition of an albumin-binding domain allows for affinity purification and in vivo half-life extension
KTH, School of Biotechnology (BIO), Protein Technology.ORCID iD: 0000-0003-1763-9073
KTH, School of Biotechnology (BIO), Protein Technology.ORCID iD: 0000-0003-1598-8894
KTH, School of Biotechnology (BIO), Protein Technology.
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2014 (English)In: Biotechnology Journal, ISSN 1860-6768, Vol. 9, no 9, 1215-1222 p.Article in journal (Refereed) Published
Abstract [en]

Emerging strategies in cancer biotherapy include the generation and application of bispecific antibodies, targeting two tumor-associated antigens for improved tumor selectivity and potency. Here, an alternative format for bispecific molecules was designed and investigated, in which two Affibody molecules were linked by an albumin-binding domain (ABD). Affibody molecules are small (6 kDa) affinity proteins and this new format allows for engineering of molecules with similar function as full-length bispecific antibodies, but in a dramatically smaller size (around eight-fold smaller). The ABD was intended to function both as a tag for affinity purification as well as for in vivo half-life extension in future preclinical and clinical investigations. Affinity-purified bispecific Affibody molecules, targeting HER2 and HER3, showed simultaneous binding to the three target proteins (HER2, HER3, and albumin) when investigated in biosensor assays. Moreover, simultaneous interactions with the receptors and albumin were demonstrated using flow cytometry on cancer cells. The bispecific Affibody molecules were also able to block ligand-induced phosphorylation of the HER receptors, indicating an anti-proliferative effect. We believe that this compact and flexible format has great potential for developing new potent bispecific affinity proteins in the future, as it combines the benefits of a small size (e.g. improved tissue penetration and reduced cost of goods) with a long circulatory half-life.

Place, publisher, year, edition, pages
2014. Vol. 9, no 9, 1215-1222 p.
Keyword [en]
Affibody molecules, Albumin-binding domain, Bispecific, Half-life extension, HER3
National Category
Biological Sciences
URN: urn:nbn:se:kth:diva-153852DOI: 10.1002/biot.201400009ISI: 000341694200013ScopusID: 2-s2.0-84906948848OAI: diva2:754866
Swedish Foundation for Strategic Research Swedish Research Council, 2012-9975Swedish Cancer Society, CAN 2013/586Vinnova

QC 20141013

Available from: 2014-10-13 Created: 2014-10-09 Last updated: 2014-10-13Bibliographically approved

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Malm, MagdalenaBass, TarekLord, MartinStåhl, StefanLöfblom, John
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