Doxorubicin antibody conjugates

Several ADEPT systems that are beyond the scope of this chapter have been studied extensively and are the subject of many reviews.15,92-93 One of the most widely cited ADEPT systems employs a glucouronidase (GUS)-monoclonal antibody conjugate that activates a doxorubicin-glu-curonide prodrug. Studies have shown that there is a substantial therapeutic benefit, a higher level of drug in tumor tissue when compared... 

Yang, H. M., and Reisfeld, R. Doxorubicin conjugated with a monoclonal antibody directed to a human melanoma-associated proteoglycan suppresses the growth of established tumor xenografts in nude mice, Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 1189-1193. 

Of the non-antibody, non-liposome based drug targeting strategies, most of the (limited) clinical experience has been obtained with polymer-based conjugates of anticancer drugs. The most widely employed drugs for this application are cytotoxic agents such as doxorubicin and... 

Jelinkova, M., Strohalm, J., Plocova, D., et al. Targeting of human and mouse T-lym-phocytes by monoclonal antibody-HPMA copolymer-doxorubicin conjugates directed against different T-cell surface antigens. J. Cont. Rel. 52 253-270, 1998. 

Sinkule JA, Rosen ST, Radosevich JA (1991) Monoclonal antibody 44-3A6 doxorubicin immimoconjugates comparative in vitro antitumor efficacy of different conjugation methods. Tumour Biol 12 198-206... 

Evaluation of immunogenicity showed that neither PKl nor PK2 elicited antibody production (173) they did not cause bone marrow toxicity at the doses used. Both conjugates displayed significantly less cardiotoxicity (a known side-effect of anthracyclines) than free doxorubicin in a Wistar rat model (174,175). 

Kovar M, Strohalm J, Etrych T, Ulbrich K, Rihova B. Star structure of antibody-targeted HPMA copolymer-bound doxorubicin. A novel type of pol3uneric conjugate for targeted drug delivery with potent antitumour effect. Bioconj Chem 2002 13 206-215. 

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