PRODUCTION OF BI-SPECIFIC MONOCLONAL-ANTIBODIES IN A HOLLOW-FIBER BIOREACTOR

In the present study we have measured the feasibility of producing high amounts of bi-specific monoclonal antibodies (MAb) for therapeutic purposes using a hollow-fibre bioreactor. We have studied the isotype composition and functional capacity of an OKT3/OV-TL 3 quadroma (IgG2a/IgG1) and we have compared the production of bi-isotypic MAb in this system with tissue culture flasks or mouse ascites. Both culture supernatant and purified bi-isotypic MAb were able to enhance the cytolytic activity of a CD8+ T cell clone against ovarian tumour cell lines, demonstrating the presence of functional bi-isotypic MAb (bi-specific MAb). The total amount of immunoglobulin produced after 38 days was 375 mg. After purification by protein A affinity chromatography, 79 mg of bi-isotypic MAb (IgG1/IgG2a) was obtained. This amount of bi-isotypic MAb was similar to the amount obtained from ascitic fluid produced by 200 mice or 38 1 of tissue culture flask supernatant.