Bioselective Cell-Cell Fusion for Antibody Production

Abstract

For the past 10 years, monoclonal antibodies have been produced in many laboratories around the world by hybridoma cells formed during the random fusion, in the presence of polyethylene glycol, of hyperim-munized mouse spleen cells and selected myeloma cells (Kohler and Milstein, 1975; Galfre et al., 1977; Galfre and Milstein, 1981). This technology has provided major advancements in the biomedical sciences. The methodology, however, has two inherent disadvantages. The first is related to the random nature of fusion of cells and the high probability of destroying, losing or simply failing to fuse the relatively rare B cell producing the desired antibody. The second disadvantage is the fact that chemically induced fusions result in very large numbers of growing colonies that need to be screened for antibody production. In cases in which the antigen in question is very rare or is in a crude form, or both, this screening process poses insurmountable problems at times. In addition, chronic hyperimmunization of the animals prior to fusion has been the standard practice, in order to stimulate and expand the appropriate subpopulations of B cells and therefore increase the chance of including these cells of interest in the group ultimately fused. This practice necessitates the use of large amounts of antigen.