In 1975 Koehler and Milstein described a method for making cell lines
that secrete a single species of antibody of desired specificity (mono
clonal antibody) (1). Hybridoma technology has permitted the productio
n of a wide range of monoclonal antibodies (mAb) for use in different
fields of basic science and clinical applications. Since 1980 the most
promising feature of mAb has been considered their potential for use
as immunotherapeutic agents. Monoclonal antibodies have found clinical
applications in the diagnosis and therapy of cancer, in the modulatio
n of the immune response, in autoimmunity and in transplantation (2-4)
. However, the promise of hybridoma technology still remains somewhat
unfulfilled and scientists and clinicians have not yet been able to fu
lly exploit the potential versatility of mAb. There are several reason
s that could contribute to the low therapeutic efficacy observed when
mAb are used in vivo. First, unmodified rodent mAb elicit a human anti
-mouse antibody immune response (HAMA). Moreover, the xenogenic nature
of the antibody may result in an immune response which limits the bio
availability and consequently, the efficacy of the antibody. Therefore
it is a human (or nearly human) Ig which is needed for clinical appli
cations, and if possible, one which displays high specificity and affi
nity for the target. Here it will be reviewed the most recent approach
es used to the production of antibodies for clinical applications.