chapter  2
18 Pages

Chapter Antibody Therapies for Liver Malignancy and Transplantation

The rst treatment of human disease with an antibody can be dated back to 1890, when an antiserum against a bacterial toxin was used to treat diphtheria.1 The success of this “immunotherapy” prompted medical communities to explore further the usefulness of antiserum or antibody therapies in the treatment of various human diseases. Disappointingly, little therapeutic success has been achieved with the administration of polyclonal antiserum because of its heterogeneous quality and potential immunogenicity in human patients. Research on antibody therapy continued, and gained momentum in 1975 with the advent of hybridoma fusion technology that enabled the production

2.1 Introduction ............................................................................................................................ 13 2.2 Antibody Engineering ............................................................................................................ 14

2.2.1 Single-Chain Variable Fragment ................................................................................ 16 2.2.2 Humanized Therapeutic Antibodies ........................................................................... 16

2.2.2.1 Mouse-Human Chimeric Antibodies .......................................................... 17 2.2.2.2 Complementarity-Determining Region-Grafted Antibodies ....................... 18 2.2.2.3 Specicity-Determining Residue-Grafted Antibodies ................................ 19

2.3 In Vitro Afnity Maturation ...................................................................................................20 2.3.1 Phage Display ............................................................................................................. 21 2.3.2 Bacterial Display ........................................................................................................ 21 2.3.3 Yeast Display ..............................................................................................................22 2.3.4 Ribosome Display .......................................................................................................22