title: Engineering antibodies for clinical applications in cancer.
abstract: The 'magic bullet' concept predicted over a century ago that antibodies would be used to target cancer therapy. Since then initial problems that were related to specificity, purity and immungenicity of antibody-based reagents have slowly been overcome due to developments in technology and increased knowledge. As a result, antibodies are in use for many clinical applications and now comprise the second largest category of medicines in clinical development after vaccines. For antibody-based cancer therapeutics the last 20 years have met with an explosion of knowledge about the biology of the disease and potential targets as well as new technology which allows cloning and manipulation of multifunctional antibody-based molecules. However, the focus still remains on developing therapeutics that will have potential for treating cancer in people and this is efficiently assessed in mechanistic clinical trials that feed back to the laboratory for further development. This review illustrates the mechanistic approach to making new molecules for antibody imaging and therapy of cancer. It is illustrated by examples of radioimmunotherapy and antibody-directed enzyme prodrug therapy developed by the authors.
authors.affiliation: Department of Oncology, Royal Free and University College Medical School, University College London, London, UK. k.chester@ucl.ac.uk
authors.forename: Kerry
authors.initials: K
authors.lastname: Chester
authors.forename: Barbara
authors.initials: B
authors.lastname: Pedley
authors.forename: Berend
authors.initials: B
authors.lastname: Tolner
authors.forename: John
authors.initials: J
authors.lastname: Violet
authors.forename: Astrid
authors.initials: A
authors.lastname: Mayer
authors.forename: Surinder
authors.initials: S
authors.lastname: Sharma
authors.forename: Geoff
authors.initials: G
authors.lastname: Boxer
authors.forename: Alan
authors.initials: A
authors.lastname: Green
authors.forename: Sylvia
authors.initials: S
authors.lastname: Nagl
authors.forename: Richard
authors.initials: R
authors.lastname: Begent
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000917:Antibody Formation; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011355:Prodrugs; D016499:Radioimmunotherapy / Q000379:methods* / Q000639:trends; D011994:Recombinant Proteins
chemical_list: D000911:Antibodies, Monoclonal; D011355:Prodrugs; D011994:Recombinant Proteins