Cover. Production of monoclonal antibodies in microfluidic devices

BOURGUIGNON, N; ATTALLAH, C; KARP, P; BOOTH, R; PEÑAHERRERA, A; PAYÉS, C; OGGERO, M; PÉREZ, M.S; HELGUERA, G; LERNER, B.

integrative biology

royal society of chemistry

Año: 2018

1757-9708

Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for theproduction of recombinant proteins is presented. The geometric configuration of the microchannels inthe device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequatemicroenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours.CHO-ahIFNa2b and HEK-ahIFNa2b adherent cell lines expressing a novel anti-hIFN-a2b recombinantmonoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on thesurface of PDMS/glass microchannels coated with poly-D-lysine. A 24 day culture of CHO-ahIFNa2b cellsresulted in MAb concentrations up to 166.4 mg mL1 per day. The productivity of CHO-ahIFNa2b andHEK-ahIFNa2b cell lines was higher in the microdevice compared to that obtained using the adherent cellculture method (T-flask), with a 5.89- and 7.31-fold increase, respectively. Moreover, biological analysisof the MAbs produced in the microdevice showed no significant differences in the neutralizingantiproliferative activity of the hIFN-a2b or the cytokine cell signaling compared to the MAbs producedwith cell adherent methods. These results suggest that this microfluidic device is suitable for long-termculture of mammalian cells and can improve the productivity of cells expressing recombinant MAbs withpotential for therapeutic use without affecting the quality attributes of the product.