Large-Scale Production of Monoclonal Antibodies

Abstract

The increased application of monoclonal antibodies in diagnostics and therapy has resulted in a demand for large quantities, grams to kilograms, to be produced. Traditionally, smaller quantities have been produced from hybridomas grown as ascites tumors in mice. However, this method is difficult to scale up and is not applicable to human hybridomas. The obvious alternative is in vitro cultures, which can be scaled up and made highly reproducible. Most culture systems have been originally designed for growth of microorganisms and do not always meet the specific demands of animal cells. Because these cells lack cell walls, they are very fragile and more sensitive to shearing forces than microorganisms. The airlift reactor is one example considered to have appropriate characteristics for shear-sensitive cells (Katinger, Scheirer, and Kromer, 1979) and has consequently been used for the production of monoclonal antibodies. Several developments have also been made to reduce the shearing forces in stirred-tank reactors while maintaining adequate oxygenation and mixing of the culture (Fazekas de St. Groth, 1983; Feder and Tolbert, 1983; Reuveny, Zheng, and Eppstein, 1986a).