Abstract
The aim of the present study was to develop the most favorable conjugation condition by evaluating the drug activity and the antibody activity of immunoconjugates consist of monoclonal antibodies and carboplatin in various ratios. The monoclonal antibodies used are 6D7, which recognizes cytokeratin-8, and 1B2, which recognizes CEA on the cell surface. Carboxymethyl dextran (MW=13, 000) was used as the carrier, which was added to the monoclonal antibody in the molar ratios from 1 : 1 to 3, 000 : 1, and then filtrated to remove uncoupled dextran molecules. And then carbopIatin was given to the mixture in the fixed molar ratio of 100 : 1, and again filtrated. In cases of both 6D7 and 1B2, the binding rate of dextran was almost stable, from 90 to 98 %, and that of carboplatin was increased from around 40 % to more than 80 %, in relation to the amount of the drug given to the antibody-dextran complex. The weight ratio of carboplatin to monoclonal antibodies were calculated, which also increased in relation to the amount of the drug given to the complex, and the maximal drug/antibody weight ratio was 626 : 1. The cell proliferation inhibition activity was evaluated by colony formation method using a human ovarian carcinoma cell line, HOC-21, whose culture medium was found to contain high amount of TPA and CEA. Immunoconjugates containing 6D7 or 1B2 showed dose-dependent inhibition activity, which was similar to unbound drug and nonspecific mouse IgG-drug conjugate. Thus, the drug activity was found not to be deranged by the conjugation procedure. The antibody activity was studied by an enzyme immunoassay using antigen-coated beads, and it was showed that, in 6D7-conjugates, the antibody activity was decreased when a large amount of drug was conjugated, while 1B2 conjugates showed a negligible change, although these changes seemed to be toretable. From the results obtained, as for the immunoconjugates we developed, the drug activity was preserved, and the decrease in the antibody activity seemed to he torelable, which should be preferable for the immunotargeting therapy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
