Lau, Achilles K. M. (1994) Synthesis and biological evaluation of novel drug-monoclonal anti-carcinoembryonic antigen antibody immunoconjugates. Masters thesis, Memorial University of Newfoundland.
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The objective of this project was to produce novel drug-monoclonal antibody immunoconjugates for site specific drug delivery. The model in these studies consisted of a target, the tumor associated carcinoembryonic antigen (CEA) expressed by a wide range of human solid tumors, and conjugates of doxorubicin (Adriamycin®) (Dox), a potent antibiotic chemotherapeutic drug, covalently linked to a monoclonal anti-CEA antibody by different heterobifunctional cross-linking reagents. -- The structure of cross-linking reagents were fully characterized by chemical spectroscopy, infrared (IR) , ¹H and ¹³C nuclear magnetic resonance (NMR), and mass spectra (MS). The spacer-Dox derivatives were also characterized by ¹H NMR before coupling to thiol groups of thiolated monoclonal anti-CEA antibody. The immunoreactivity of immunoconjugates was evaluated by enzyme linked immunosorbent assays (ELISAs) which showed that all immunoconjugates retained specific binding to CEA. The efficacy of immunoconjugates was determined in MTT (3-4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide) cell survival assays. The Dox 3'-N-amide linked immunoconjugates are not very active in vitro with CEA expressing cell lines. However, the Dox C-13 hydrazone linked immunoconjugates are active in vitro.
|Item Type:||Thesis (Masters)|
|Additional Information:||Bibliography: leaves 206-228.|
|Department(s):||Pharmacy, School of|
|Library of Congress Subject Heading:||Antibody-drug conjugates; Monoclonal antibodies; CEA (Oncology); Doxorubicin; Cancer--Immunology|
|Medical Subject Heading:||Antibodies, Monoclonal; Neoplasms--immunology; Carcinoembryonic Antigen; Doxorubicin; Immunoconjugates|
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