Targeted chemotherapy : evaluation of monoclonal anti-CEA antibody drug conjugate efficacy

Casson, Alan Graham (1985) Targeted chemotherapy : evaluation of monoclonal anti-CEA antibody drug conjugate efficacy. Masters thesis, Memorial University of Newfoundland.

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Abstract

Targeted chemotherapy, a potentially clinically relevant method of increasing the selective delivery of cytotoxic agents to tumor cell populations has been evaluated. -- The model used in these studies comprised a target, the tumor associated carcinoembryonic antigen, which is expressed by a wide range of human solid tumors, and conjugates of vindesine, a potent vinca alkaloid, covalently linked to a specific monoclonal anti-CEA antibody. -- Characterisation of human tumor cell lines by immunocytochemistry and radiobinding assays established a range of CEA expression enabling selected cell lines to be used for the assessment of conjugate efficacy in vitro, and to be grown as xenografts in nude mice enabling a relevant pre-clinical model to be developed. The effect of conjugate treatment upon the growth of xenografts with a range of CEA expression was then assessed. -- These studies demonstrated the efficacy and selectivity of immunochemotherapy both in vitro and in vivo using this model, confirming theoretical predictions. In addition, prolonged survival of mice treated with conjugate and reduced toxicity of conjugated compared to free drug was demonstrated in one experimental protocol. -- Further investigations and the clinical potential of this approach are discussed.

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