The Immunogenicity of Therapeutic Antibodies

The story of immunogenicity of therapeutic antibodies started with the production of murine antibodies. They showed immunogenic behavior due to their foreignness to the human immune system and that was expected. With the advancements in antibody engineering, therapeutic antibodies became more human, with the latest generation of fully human antibodies. Though there was a trend in decreased immunogenicity from murine to fully human antibodies, immunogenic events were still reported. This chapter will summarize the current status of antibody development, lay the basis for general immunogenicity and immunogenicity of therapeutic antibodies in specific and describe the clinical impact of antibody immunogenicity. Furthermore, the bioanalytical assessment, prediction and reduction of immunogenicity will be presented. The chapter will end with an outlook into antibody-based next generation therapeutics and what we may (or may not) expect in terms of immunogenicity.