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Expression and characterization of recombinant antibody fragments against hepatocellular carcinoma

Authors Chu, Siu Hong
Issue Date 1999
Summary Hepatocellular carcinoma (HCC) is one of the most severe malignancies in the world. It causes an estimated l,OOO,OOO deaths every year worldwide. HCC is one of the most commnon causes of cancer death in South Asia and Africa and is the second most common in Hong Kong. Most HCC patients die within four months after being diagnosed as having HCC. Surgery is the only curative modality for HCC but it is applicable in a very small number of patients. Chemotherapy is ineffective against HCC, partly due to the lack of specificity and high toxicity of the treatments. Immunotherapy is a novel approach for liver cancer treatment. Using liver cancer cell specific antibodies to carry therapeutic agents can enhance the effects of chemotherapy and reduce the dosage of toxic chemical used in the treatment. Anti-HCC monoclonal antibodies were raised in mouse and hybridomas were selected for the production of antibodies against HCC. A hybridoma, designated hybridoma 95, was screened for its production of mAb targeting HCC with high specificity. The mAb, designated mAb95, had been shown to target HCC cells in a highly specific manner. However, mouse mAbs cannot be used directly in humans because of their high immunogenicity, which causes adverse side effects known as Human Anti Mouse Antibody (HAMA) reactions. In my study, antibody fragments were designed which retain the binding specificity of mAb95 but were potentially less immunogenic than the original mAb. Two antibody fragments derived from mAb95 were designed and expressed in E.coli. Both antibody fragments had been found to possess the same binding specificity as the original anti-HCC mAb95. Mutational analysis had been performed. It was found that the position 99 on the heavy chain variable region is critical for antigen binding in this particular antibody
Note Thesis (M.Phil.)--Hong Kong University of Science and Technology, 1999
Language English
Format Thesis
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