Abstract
Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10 g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for e...Continue Reading
References
Aug 13, 1993·Cell·J H ChungG Felsenfeld
Jul 8, 2000·Animal Biotechnology·C CammusoW Gavin
Oct 24, 2001·Current Opinion in Oncology·E S KimR S Herbst
May 3, 2002·The Journal of Biological Chemistry·Robert L ShieldsLeonard G Presta
Jan 28, 2003·Nature Biotechnology·Brigid BrophyGötz Laible
Sep 2, 2003·Trends in Biotechnology·Michael K DyckMarc-André Sirard
Apr 20, 2005·Cancer Cell·Shiqing LiKathryn M Ferguson
Aug 25, 2005·Clinical Therapeutics·Siu-Fun Wong
Aug 11, 2006·Nature Biotechnology·Charlie Schmidt
Feb 5, 2008·Comparative Immunology, Microbiology and Infectious Diseases·Louis-Marie Houdebine
Mar 14, 2008·The New England Journal of Medicine·Christine H ChungThomas A E Platts-Mills
Apr 9, 2009·Nature Biotechnology·Jim Kling
May 26, 2009·Biotechnology Advances·David L HackerFlorian M Wurm
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Sep 10, 2009·Clinical and Experimental Immunology·E MartinelliF Ciardiello
Nov 6, 2009·Current Opinion in Biotechnology·Yves Durocher, Michael Butler
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jul 13, 2011·Nature Biotechnology·Jeroen J Lammerts van BuerenPaul W H I Parren
Sep 22, 2012·Journal of Biotechnology·Harrie A van VeenMaurice L M Mannesse
Dec 25, 2012·Nature Biotechnology·Yang DongWen Wang
Jan 1, 2012·Oncogenesis·F HenjesU Korf
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Oct 10, 2014·Nature Biotechnology·Gary Walsh
Mar 10, 2015·The Journal of Allergy and Clinical Immunology·John W SteinkeScott P Commins
Apr 9, 2016·Molecular Immunology·Marco ThomannMax L Tejada
Feb 22, 2018·ESMO Open·Walter FiedlerLuca Gianni
Sep 6, 2018·Scientific Reports·Ran ZhangNing Li