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

Bohrmann, Bernd
Kopetzki, Erhard
Schweitzer, Christoph
Jacobsen, Helmut
Moniatte, Marc
Aebischer, Patrick
Schneider, Bernard L
Published in Biomaterials. 2014, vol. 35, no. 2, p. 792-802
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 in the plasma.
Keywords AnimalsCell LineCells, Immobilized / cytologyCloning, MolecularDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayGenetic Engineering / methodsGenetic TherapyGenetic VectorsGlycosylationHumansImmunoglobulin G / administration & dosageLentivirus / geneticsMiceMyoblasts / cytologyPromoter Regions, GeneticRecombinant Proteins / administration & dosageSubcutaneous Fat / metabolismTransgenes
PMID: 24344356
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LATHUILIERE, Aurélien et al. Genetic engineering of cell lines using lentiviral vectors to achieve antibody secretion following encapsulated implantation. In: Biomaterials , 2014, vol. 35, n° 2, p. 792-802. doi: 10.1016/j.biomaterials.2013.10.026

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Deposited on : 2021-11-01

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