Genetic engineering of cell lines using lentiviral vectors to achieve antibody secretion following encapsulated implantation

Biomaterials
Aurélien LathuilièreBernard Laurent Schneider

Abstract

The controlled delivery of antibodies by immunoisolated bioimplants containing genetically engineered cells is an attractive and safe approach for chronic treatments. To reach therapeutic antibody levels there is a need to generate renewable cell lines, which can long-term survive in macroencapsulation devices while maintaining high antibody specific productivity. Here we have developed a dual lentiviral vector strategy for the genetic engineering of cell lines compatible with macroencapsulation, using separate vectors encoding IgG light and heavy chains. We show that IgG expression level can be maximized as a function of vector dose and transgene ratio. This approach allows for the generation of stable populations of IgG-expressing C2C12 mouse myoblasts, and for the subsequent isolation of clones stably secreting high IgG levels. Moreover, we demonstrate that cell transduction using this lentiviral system leads to the production of a functional glycosylated antibody by myogenic cells. Subsequent implantation of antibody-secreting cells in a high-capacity macroencapsulation device enables continuous delivery of recombinant antibodies in the mouse subcutaneous tissue, leading to substantial levels of therapeutic IgG detectable i...Continue Reading

References

Nov 5, 1997·Nature Biotechnology·R ZuffereyD Trono
Jun 13, 2001·Gene Therapy·B L SchneiderP Aebischer
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 5, 2005·Trends in Biotechnology·Maciej Wiznerowicz, Didier Trono
May 10, 2005·Biotechnology and Bioengineering·Diane M Dinnis, David C James
Sep 22, 2005·Nature Reviews. Microbiology·Frederic BushmanChristian Hoffmann
Dec 3, 2005·Biotechnology Progress·Jason HodoniczkyDavid C James
Jan 9, 2007·Molecular & Cellular Proteomics : MCP·Morten Thaysen-AndersenPeter Højrup
Apr 3, 2007·Journal of Neuroscience Methods·Elizabeth E CapowskiClive N Svendsen
Apr 28, 2007·Biotechnology and Bioengineering·Deborah E PascoeDana C Andersen
Jun 6, 2009·Glycobiology·Patrick HosslerZheng Jian Li
Feb 10, 2010·Archivum Immunologiae Et Therapiae Experimentalis·David Escors, Karine Breckpot
Jul 1, 2010·Biotechnology and Bioengineering·Peter M O'CallaghanDavid C James
Jul 14, 2010·MAbs·Feng LiAshraf Amanullah
Sep 3, 2010·Nature Reviews. Drug Discovery·Aaron L NelsonJanice M Reichert
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kang ZhangGeorge A Williams

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Citations

May 27, 2015·International Journal of Molecular Sciences·Aurélien LathuilièreBernard L Schneider
Mar 10, 2016·Brain : a Journal of Neurology·Aurélien LathuilièrePatrick Aebischer
Jun 23, 2016·Advanced Healthcare Materials·Ana Catarina LimaJoão F Mano
Jan 26, 2017·Médecine sciences : M/S·Aurélien Lathuilière, Bernard L Schneider
Dec 29, 2017·Advanced Healthcare Materials·Christophe BossUmberto De Marchi
Nov 24, 2020·Acta Neuropathologica Communications·Vanessa LaversenneBernard L Schneider

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