Circumventing immunogenicity in the development of therapeutic antibodies.
The development of anti-therapeutic antibody immune responses can limit efficacy and reduce the safety of antibody treatments. Despite significant advances to minimize such immune responses, these responses still occur, even against fully human antibodies. Thus, the ability to assess the immunogenic potential of a therapeutic antibody can provide significant benefits during the development cycle of a therapeutic protein, and may lead to the future development of therapeutic antibodies that possess minimal immunogenicity. In particular, in vitro, in silico and ex vivo methods have been developed for the prediction of T-cell epitopes that can lead to immunogenicity. Ultimately, immunogenicity may be completely avoided by the generation of humanized or fully human non-immunogenic therapeutic antibodies using techniques such as deimmunization and composite human antibodies.
Holgate
Robert G E
RG
Antitope Ltd, Babraham Research Campus, Babraham, Cambridge, CB22 3AT, UK. rob.holgate@antitope.co.uk
Baker
Matthew P
MP
D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000917:Antibody Formation; D015195:Drug Design; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans
D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte