Selecting and Evolving Therapeutic Human Antibodies

To test this hypothesis, we created the first synthetic antibody libraries in 1992 (Barbas et al., 1992). In this study a repertoire of synthetic 

Immune libraries and evolutionary selection strategies intersect in the area of antibody humanization. Recently, we have extended the repertoire of methods available for the generation of therapeutic human antibodies by developing phage display strategies for the selection and humanization of antibodies from immune animals other than mice. Our aim here was to modify protein sequence, in some cases in a very radical way, and yet retain the function of the parental antibody. In the following discussion, we will focus on these novel approaches. 

More than twenty years of rodent monoclonal antibody generation by the classical hybridoma technology has yielded a number of promising therapeutic candidates and their humanization compares well to the de novo generation and characterization of human antibodies for accessing clinical applications in the coming years. 

In contrast to human antibodies derived from large naive or synthetic human antibody libraries, antibodies from immune animals were subjected to in vivo selection and are therefore more likely to recognize a given antigen selectively (i.e., without cross-reactivity to another antigen). 

Although until recently antibody humanization was based on arduous rational design strategies that require computer modeling and itera- 

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