Process development of periplasmatically produced single chain fragment variable against epidermal growth factor receptor in Escherichia coli

2014 ◽  
Vol 192 ◽  
pp. 136-145 ◽  
Author(s):  
Robert Lindner ◽  
Anna Moosmann ◽  
Alexander Dietrich ◽  
Heiner Böttinger ◽  
Roland Kontermann ◽  
...  
2021 ◽  
Vol 17 (3) ◽  
pp. 447-455
Author(s):  
Ling Ni ◽  
You-Xin Li

Purpose: Although monoclonal antibodies are used to decorate nanoparticles to target specific cells, penetration of tumor tissues by monoclonal antibodies is limited by their large size. Therefore, we prepared DM1 nanoparticles decorated with the small anti-HER2 single-chain Fv fragment (scFvHER2) of trastuzumab (TMAB) for targeting to human epidermal growth factor receptor 2 (HER2) overexpressing in breast cancer effectively. Methods: ScFvHER2 fragment was coupled with DM1 nanoparticles (NPs) via covalent thiol-maleimide linkages. Their physicochemical properties, uptake by cells, and toxicity to tumor cells were investigated. Their vivo biodistribution was assessed employing liquid chromatographytandem mass spectrometry, while their antitumor activity was investigated in nude mice burdened with BT-474 tumor. Results: Viability of BT-474 cells incubated with scFvHER2-DM1-Nanoparticles (scFv-DM1-NPs) was significantly lower than that of BT-474 cell treated with TMAB-DM1-Nanoparticles (TMAB-DM1-NPs) (P < 0 05). Uptake by cells of scFvDM1-NPs was significantly higher than TMAB-DM1-NPs (P < 0 01). Accumulation of scFv-DM1-NPs in tumor tissue was notably higher than TMAB-DM1-NPs (P < 0 05). scFv-DM1-NPs exhibited improved antitumor effects compared to TMABDM1-NPs (P < 0 05), showing a tumor inhibition rate of more than 70%. Conclusions: ScFvHER2 fragment could serve as a more effective targeting ligand than TMAB, and scFv-DM1-NPs could be developed as a possible drug delivery system to target HER2-positive breast cancer.


2019 ◽  
Vol 23 (3) ◽  
pp. 382-388 ◽  
Author(s):  
Yong Tao ◽  
Nandell F. Keene ◽  
Kristin E. Wiglesworth ◽  
Barbara Sitter ◽  
J. Christopher McWilliams

2011 ◽  
Vol 109 (6) ◽  
pp. 1461-1470 ◽  
Author(s):  
Mariusz P. Madej ◽  
Gregory Coia ◽  
Charlotte C. Williams ◽  
Joanne M. Caine ◽  
Lesley A. Pearce ◽  
...  

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