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Chimerization and Humanization

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Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology. However, mouse mAbs cannot be used for therapy in human due to their immunogenicity. Advances in chimerization and humanization technologies have dramatically improved the performance of mAbs. Recently the use of human antibody-producing transgenic mice and phage display technologies have allowed the development of fully human mAbs.

Chimeric antibodies are made by fusing variable domains from one species, such as a mouse, with constant domains from another species, such as a human being. With such biotechnical manipulation, chimeric antibodies retain the foreign antibody’s antigen specificity and affinity. The development of chimeric and humanized mAbs is facilitated by molecular biology tools like recombinant DNA and fusion technology (not shown here) Note that a fusion protein is a protein consisting of at least two domains that are encoded by separate genes that have been joined as a single unit Structural modifications such as glycosylation and pegylation are introduced herein as formulation factors

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Pharmacotherapy: Understanding Biotechnology Products

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