The development of hybridoma technology for producing monoclonal antibodies (mAbs)\nby Kohler and Milstein (1975) counts as one of the major medical breakthroughs, opening up endless\npossibilities for research, diagnosis and for treatment of a whole variety of diseases. Therapeutic\nmAbs were introduced three decades ago. The first generation of therapeutic mAbs of murine\norigin showed high immunogenicity, which limited efficacy and was associated with severe infusion\nreactions. Subsequently chimeric, humanized, and fully human antibodies were introduced as\ntherapeutics, these mAbs were considerably less immunogenic. Unexpectedly humanized mAbs\ngenerally show similar immunogenicity as chimeric antibodies; based on sequence homology chimeric\nmAbs are sometimes more â??humanâ? than humanized mAbs. With the introduction of the regulatory\nconcept of similar biological medicines (biosimilars) a key concern is the similarity in terms of\nimmunogenicity of these biosimilars with their originators. This review focuses briefly on the\nmechanisms of induction of immunogenicity by biopharmaceuticals, mAbs in particular, in relation\nto the target of the immune system.
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