Abstract
Doxorubicin (adriamycin) was conjugated via the dextran bridge method to a murine IgG3 monoclonal antibody, 1G3.10, directed against human bladder cancer. The drug-antibody conjugate, prepared from using 25% oxidized dextran as the linker, retained essentially the original immunological activity of the antibody using ELISA as tested against an antigen-positive target cell line (TSGH-8301), which has been shown to express an antigen recognized by the monoclonal antibody 1G3.10. Antitumor effect of the conjugate in vitro was evaluated by its inhibition on 3H-uridine incorporation into the established human bladder cancer cells. The conjugate exhibited a significantly higher cytotoxicity on target TSGH-8301 cells than that by a control antibody-doxorubicin conjugate prepared identically from an irrelevant mouse IgG3 monoclonal antibody. No apparently different cytotoxicity was detected on control antigen-negative bladder tumor cells of J82 between these two drug-antibody conjugates. Verapamil, a calcium channel blocker, enhanced the in vitro cytotoxicity of doxorubicin-1G3.10 monoclonal antibody conjugate. Results obtained from in vivo evaluation using xenografted target TSGH-8301 bladder tumor indicated that the 1G3.10 monoclonal antibody conjugate containing doxorubicin injected 4×, i.p., significantly inhibited TSGH-8301 bladder tumor growth in nude mice, whereas free monoclonal antibody, free drug and the mixture of both showed only moderate inhibition of tumor growth as compared to the untreated control. Verapamil also enhanced in vivo antitumor activity of the conjugate. There was no side effect (weight loss) detected on the conjugate-treated mice. Results obtained from in vivo evaluation using xenografted control J82 bladder tumor showed no specific antitumor activity as exhibited by doxorubicin-1G3.10 monoclonal antibody conjugate in comparison with free drug, mixture of drug and antibody without conjugation, or doxorubicin conjugated to the irrelevant antibody. These results suggested that doxorubicin conjugated with bladder tumor associated monoclonal antibody could be useful as a potentially cytotoxic agent in immunochemotherapy of human bladder cancer.
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.
