MONOCLONAL-ANTIBODIES - APPLICATIONS IN H EMATOLOGY

Since its discovery at the end of the last century, antibodies have be en considered useful analytical tools because of its exquisite specifi city. However, the tremendous practical potential of these reagents fo r applications in biology, medicine and industry was fully realized af ter the introduction by Kohler and Milstein of the methodology for the in vitro production of antibodies with a predetermined specificity in 1975 (The advent of monoclonal antibodies). Monoclonal antibodies can be produced al large scale, almost pure and its chemical structure is well known, allowing multiple applications. The earliest uses of mono clonal antibodies were related to histocompatibility tests and the rec ognition of surface molecules associated with normal and tumor cells, leading to a more efficient cell typing. Its use for the recognition o f specific epitopes on virus, bacteria and other microorganisms or in molecules like proteins, carbohydrates, nucleic acids, etc., has been the basis for numerous diagnostic and industrial applications. This ha s led to the development of a great variety of diagnostic ELISA and ra dioimmunoassay tests, resulting in a more accurate identification of m icroorganisms for diagnosis and epidemiology. It also caused a more de tailed knowledge of different cellular subsets and the stages of diffe rentiation of cells in specific tissues. The original technique descri bed by Kohler and Milstein allows the production of murine monoclonal antibodies. These murine reagents are used successfully in the biomedi cal field. Unfortunately, its use in therapeutic applications and in t he in vivo diagnosis of human diseases has been limited. The main reas ons for this limitation appear to be an accelerated removal and/or fun ction impairment of the murine monoclonal reagents caused by the exist ence in man of ''natural'' anti-mouse antibodies and by the developmen t of a humoral human anti-mouse immunoglobulin response secondary to t he administration of these reagents for the development of techniques suited for the production of monoclonal antibodies mouse monoclonal an tibodies to humans. This limitation also has been the major driving fo rce of human origin expecting that, when administered in prophylactic, therapeutic or in vivo diagnostic protocols, these human reagents res ult less immunogenic than those coming from mice. The potential use of human monoclonal antibodies includes fields like cancer treatment, tu mor imagenology and organ transplantation, among others. Unfortunately , the generation of human monoclonal antibodies using procedures analo gous to those used in the mouse model had been fruitless, numerous tec hnical problems had been faced and the literature in the field is full of different methods and ''improvements.'' Two main ways are currentl y in use for the production of human monoclonal antibodies. One is the immortalization of the antibody producer cells, which is achieved by Epstein-Barr virus transformation of a lymphocytes and/or by hybridoma generation. More recently, molecular biology techniques are being ada pted and used as very powerful and promising tools for the preparation , modification and improvement of monoclonal antibodies from either mu rine or human origin. These two approaches, independently or combined, are currently in use in laboratories all over the world to produce mo noclonal reagents to be used in the effective prevention, treatment an d diagnosis of human diseases.