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European Biopharmaceutical Review

The Antibody Effect

Richard Buick, Nicolas Camper and Chris Scott at Fusion Antibodies discuss how monoclonal antibodies are the fastest-growing sector of the therapeutic market, yet are also one of the most expensive drugs per dose due to their high manufacturing costs

An average patient’s treatment with Avastin costs $55,000 per year and could rise to as high as $100,000 per year for some cases, as quoted in Pharmacy Times, 19th October, 2006. In order to keep these costs down, the maximum yield of antibody per litre of culture is being pushed ever higher, and current cell lines are reported that express more than 10 grams of antibody per litre of culture. In this article, we report on the various expression systems that have been used to optimise production of recombinant antibodies, and consider the next evolution of cell line development that may emerge to increase cell productivity.

ENGINEERING ANTIBODIES

Isolation and characterisation of the primary structure of the antibody is required in order to engineer a recombinant antibody. Antibodies are complex proteins consisting of two heavy chains and two light chains held together by disulphide bonds. Each chain has a variable region which is involved in binding other proteins. It is this variability that allows antibodies to recognise such a wide range of biomarker targets. Initial cloning of antibody-variable genes started over 20 years ago with the construction of libraries of genomic DNA from antibody-expressing cells (B-cells, hybridomas, and B-tumour cell lines) (1,2). This procedure required the identification of functionally rearranged antibody genes and included intronic sequences between signal peptides, variable domains and constant domains. Reverse transcription of RNA from antibody-expressing cells into cDNA has simplified the procedure by avoiding non-rearranged genes and introns.


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Richard Buick is Technical Director of Fusion Antibodies Ltd and has nine years’ industrial experience in the recombinant antibody field. His PhD from Queen’s University, Belfast, was in engineeering antibody therapeutics for cancer. At Fusion Antibodies he manages client projects and in-house recombinant research projects.

Nicolas Camper is currently working towards his PhD at Queen’s University, Belfast, in the schools of Pharmacy and Chemistry. He has expressed and purified an antibody Fab’ from CHO cells for conjugation studies during his research in collaboration with Fusion Antibodies.

Chris Scott is a lecturer in Biomolecular Science at the School of Pharmacy, Queen’s University, Belfast. He has broad expertise in a wide range of protein expression and capture methodologies. Chris has a PhD in Biochemistry and was an original member of the scientific research team at Fusion Antibodies Ltd. In 2003, Chris joined Queen’s to establish his research team focusing the development of novel antibody-based therapeutic strategies for the treatment of cancer.

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Richard Buick
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Nicolas Camper
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Chris Scott
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