Production methods for generating human monoclonal antibodies

Abstract

The technology explosion that mushroomed from the uses and applications of monoclonal antibodies (MAbs; Re~. 1) .shows. no signs of slowing down. Virtually the entIre bIOmedIcal arena has been transformed with the introduction of the MAb as a routine reagent in both the laboratory and clinic. The promise of MAbs has been their pote~tial selectivity and exquisite specificity. One of the ObVIOUS goals of MAb technology is to develop clinically useful human MAbs (HMAbs). Historically, the first immortalized human cell secreting specific antibody was generated by infection with a ~-tropic Epstein-Barr virus (EBV) in 19772 and the first true human-human hybridoma secreting specific antibody was described in 1980.3 Although the HMAb field was slow to take off (see below), the progress made wit~ murine MAbs has been astonishing. Clearly, the antIbody of the 1980s was of mouse origin. Whatever c.ould h~v~ been done to a MAb was attempted at this tIme: chmcal protocols, simple and elaborate chemical modifications, and some very interesting molecular biology approaches. Unfortunately, the clinical usefulness of murine MAbs has been very disappointing, due for the most part to th~ innate foreigness and immunogenicity of the mouse Immunoglobulin protein, resulting in allergic respon~es,. hepati~ dysfunctions, and immune complex formatIon m the kIdney. With the ultimate aim of trying to control and eventually eradicate human diseases thro~gh immunomodulation and to improve our ability to diagnose abnormalities, it is believed that HMAbs will prove far superior than those of murine origin. H~Abs should be more effective because of their ability to mteract more appropriately with human complement or human effector cells. In addition, HMAbs would not only be less immunogenic, but they may also recognize a se~ of allogenic antigens that are not recognized by munne MAbs. As such, the antibody of the 1990s will