MONOCLONAL-ANTIBODIES - APPLICATIONS IN HEMATOLOGY

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MONTANO, RF
ROMANO, EL
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Q14 [生态学(生物生态学)];
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071012 ; 0713 ;
摘要
Since its discovery at the end of the last century, antibodies have been considered useful analytical tools because of its exquisite specificity. However, the tremendous practical potential of these reagents for applications in biology, medicine and industry was fully realized after 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 monoclonal antibodies were related to histocompatibility tests and the recognition of surface molecules associated with normal and tumor cells, leading to a more efficient cell typing. Its use for the recognition of 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 has led to the development of a great variety of diagnostic ELISA and radioimmunoassay tests, resulting in a more accurate identification of microorganisms for diagnosis and epidemiology. It also caused a more detailed knowledge of different cellular subsets and the stages of differentiation of cells in specific tissues. The original technique described by Kohler and Milstein allows the production of murine monoclonal antibodies. These murine reagents are used successfully in the biomedical field. Unfortunately, its use in therapeutic applications and in the in vivo diagnosis of human diseases has been limited. The main reasons for this limitation appear to be an accelerated removal and/or function impairment of the murine monoclonal reagents caused by the existence in man of ''natural'' anti-mouse antibodies and by the development of a humoral human anti-mouse immunoglobulin response secondary to the administration of these reagents for the development of techniques suited for the production of monoclonal antibodies mouse monoclonal antibodies to humans. This limitation also has been the major driving force of human origin expecting that, when administered in prophylactic, therapeutic or in vivo diagnostic protocols, these human reagents result less immunogenic than those coming from mice. The potential use of human monoclonal antibodies includes fields like cancer treatment, tumor imagenology and organ transplantation, among others. Unfortunately, the generation of human monoclonal antibodies using procedures analogous to those used in the mouse model had been fruitless, numerous technical problems had been faced and the literature in the field is full of different methods and ''improvements.'' Two main ways are currently 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 adapted and used as very powerful and promising tools for the preparation, modification and improvement of monoclonal antibodies from either murine or human origin. These two approaches, independently or combined, are currently in use in laboratories all over the world to produce monoclonal reagents to be used in the effective prevention, treatment and diagnosis of human diseases.
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页码:194 / 203
页数:10
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