基因工程抗体及发展前景.ppt

The Evolution of Therapeutic Antibodies humanization-CDR grafting CDR residues from variable region of a mouse mAb are transferred to human antibody frameworks that have high sequence homology with the mouse counterparts humanization-advantage Murine mAbs have been extensively characterized and have desirable antiviral properties and/or superior fully human mAbs are hardto obtain. This viable approach is the classic and simplest strategy of humanization among many other available strategies, such as grafting specificity determining residues17. The fact that nearly half of all US Food and Drug Administration (FDA)-approved therapeutic mAbs are humanized antibodies testifies to their safety and tolerance by humans. Transgenic mouse-advantage Have a repertoire of fully human IgG1 gave researchers an alternative route to human mAbs through active immunization, without the protocol restrictions associated with human studies. Transgenic mouse-drawbacks As the immune response in transgenic mice is sometimes less robust than in strains that are used to generate mouse mAbs, more immunizations or antibody screens are often required. These transgenic mice cannot exactly reproduce the human antibody response because of repertoire differences and because the genetic background ofthe murine host affects antigen processing, B-cell ontology and regulation (e.g.,tolerance mechanisms). At present, these transgenic mice are protected intellectual property and therefore not commonly available Display technologies-strategy Phage Display - drawback Unnatural pairings of the antibody heavy and light chain components The method of presentation of antigen as bait for panning may affect the number and distribution of available neutralizing epitopes. B cell immortalization:EBV Transformation Epstein-Barr virus When EBV infects B-lymphocytes in vitro, lymphoblastoid cell lines eventually emerge that are capable of indefinite growth. The growth transformation of th