Potent and specific fusion toxins consisting of a HER2‑binding, ABD‑derived affinity protein, fused to truncated versions of Pseudomonas exotoxin A.

Published on Jul 1, 2019in International Journal of Oncology3.899
· DOI :10.3892/IJO.2019.4814
Hao Liu21
Estimated H-index: 21
(KTH: Royal Institute of Technology),
Hao Liu4
Estimated H-index: 4
(KTH: Royal Institute of Technology)
+ 6 AuthorsTorbjörn Gräslund21
Estimated H-index: 21
(KTH: Royal Institute of Technology)
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Abstract
Potent and specific fusion toxins consisting of a HER2-binding ABD-derived affinity protein (ADAPT), fused to truncated versions of Pseudomonas exotoxin A
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#1Haozhong DingH-Index: 3
#2Tianqi XuH-Index: 2
Last. Anzhelika VorobyevaH-Index: 10
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Affibody molecules hold great promise as carriers of cytotoxic drugs for cancer therapy due to their typically high affinity, easy production, and inherent control of the drug molecules' loading and spatial arrangement. Here, the impact of increasing the drug load from one to three on the properties of an affibody drug conjugate targeting the human epidermal growth factor receptor 2 (HER2) was investigated. The affibody carrier was recombinantly expressed as a fusion to an albumin-binding domain...
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#1Emma von Witting (KTH: Royal Institute of Technology)H-Index: 4
#2Sarah Lindbo (KTH: Royal Institute of Technology)H-Index: 8
Last. Sophia Hober (KTH: Royal Institute of Technology)H-Index: 41
view all 11 authors...
Albumin-binding fusion partners are frequently used as a means for the in vivo half-life extension of small therapeutic molecules that would normally be cleared very rapidly from circulation. However, in applications where small size is key, fusion to an additional molecule can be disadvantageous. Albumin-derived affinity proteins (ADAPTs) are a new type of scaffold proteins based on one of the albumin-binding domains of streptococcal protein G, with engineered binding specificities against nume...
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#1Javad Garousi (Uppsala University)H-Index: 13
#2Emma von Witting (KTH: Royal Institute of Technology)H-Index: 4
Last. Sophia Hober (KTH: Royal Institute of Technology)H-Index: 41
view all 11 authors...
Abstract Molecular recognition in targeted therapeutics is typically based on immunoglobulins. Development of engineered scaffold proteins (ESPs) has provided additional opportunities for the development of targeted therapies. ESPs offer inexpensive production in prokaryotic hosts, high stability and convenient approaches to modify their biodistribution. In this study, we demonstrated successful modification of the biodistribution of an ESP known as ADAPT (Albumin-binding domain Derived Affinity...
1 CitationsSource
#1Tianqi XuH-Index: 2
#2Haozhong DingH-Index: 3
Last. Torbjörn GräslundH-Index: 21
view all 7 authors...
The human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in a variety of cancers and therapies targeting HER2 are routinely used in the clinic. Recently, small engineered scaffold proteins, such as affibody molecules, have shown promise as carriers of cytotoxic drugs, and these drug conjugates may become complements or alternatives to the current HER2-targeting therapies. Here, we investigated if a monovalent HER2-binding affibody molecule, ZHER2:2891, fused with a plasma ...
1 CitationsSource
#1Haozhong Ding (KTH: Royal Institute of Technology)H-Index: 3
#2Mohamed Altai (Lund University)H-Index: 19
Last. Torbjörn Gräslund (KTH: Royal Institute of Technology)H-Index: 21
view all 11 authors...
The human epidermal growth factor receptor 2 (HER2) is a clinically validated target for cancer therapy, and targeted therapies are often used in regimens for patients with a high HER2 expression level. Despite the success of current drugs, a number of patients succumb to their disease, which motivates development of novel drugs with other modes of action. We have previously shown that an albumin binding domain-derived affinity protein with specific affinity for HER2, ADAPT6, can be used to deli...
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