STUDY ON THE DEVELOP OF IDIOTYPIC ANTIBODY TO ESTROGEN AND ON THE APPLICATION IT TO CLINICAL USE

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In 1974, Niels Jerne proposed a theory which pictured the immune system as a network of interacting idiotypes. This network theory of immune response emphasized the need to consider individual immunoglobulin molecules as expressing two critical sets through which they interacted with other elements of the immune system. Each molecule bears a combining site through which it interacts with conventional antigenic determinants and with other immunoglobulin molecules which bore idiotypic determinants cross-reacting with antigen. Jerne designated the antigen-combining sites of immunoglobulins as paratopes. The antigenic determinants of conventional antigens are referred to as epitopes. Each immunoglobulin molecule expresses one, or many, antigenic determinants determined by the structure of its variable regions and thus unique to it, or at least shared by only a relatively limited number of immunoglobulin molecules. These idiotypic determinants were termed as idiotopes. on the bases on these … More situation, we tried to make idiotypic antibodies that bind to estrogen receptor.We speculated that some of them should have biological activity as estrogen has. The idiotypic antibodies would be a good tool to analyze estrogen receptors in cells and be a useful medicine, which are immunoglobulin but not steroid structure, for clinical fields. First of all, we made polyclonal and monoclonal antibodies to estrogen. Then the estrogen antibodies were injected to mice to rise idiotypic antibody, that is, anti-anti-estrogen immunoglobulin. After giving several boosters, mouse spleen cells were collected and fused with mouse myeloma cells to make hybridoma producing the idiotypic antibody. The idiotypic activity was checked by the enzyme-linked immunosorbant assay (ELISA) and the binding inhibition of ^3H-estrogen to estrogen antibody. We tried several cell fusion and got thousands of hybridomas and more than one hundred monoclonal cells producing substances having estrogen like activity. We further more analyzed the biological, biochemical and chemical characteristics of these substances. The biological activity using in vivo and in vitro showed estrogen-like activity, however, biochemical analysis showed that the substance was not immunoglobulins and was lower molecular weight chemicals. We finally concluded that the substance was estrogen itself by HPLC and mass spectrography.These finding is very exciting one that high percentages of hybridoma have an ability to synthesize estrogen in vitro. Less