The clinical efficacy of therapeutic antibodies is recognized in many indications,explaining their rapid rise in the worldwide drug market.However,therapeutic antibodies can be immunogenic by inducing a specific immun...The clinical efficacy of therapeutic antibodies is recognized in many indications,explaining their rapid rise in the worldwide drug market.However,therapeutic antibodies can be immunogenic by inducing a specific immune response characterized by the production of anti-drug antibodies(ADAs).ADAs can potentially increase the clearance of therapeutic antibodies,decrease their therapeutic effects1 and induce hypersensitivity reactions.Because humans are thought to be tolerant to their own proteins,sequences of the therapeutic antibodies have been humanized or human antibodies have been directly generated by technologies using human sequences.However,human(ized)antibodies exhibit highly variable levels of immunogenicity,1,2 illustrating the poor understanding of the role of sequence humanization in mitigating the immunogenicity of therapeutic antibodies.Multiple lines of evidence highlight the role of CD4 T lymphocytes during the initiation of an ADA response,3 but few T-cell epitopes of marketed therapeutic antibodies have been described to date.展开更多
基金The research leading to these results was supported by the lInnovative MedicinesInitiative Joint Undertaking ABIRISK project under grant agreement#115303theresources of which comprise financial contribution from the European Union's Seventh Framework Programme(FP7/2007-2013)+1 种基金in-kind contributions from EFPIA companiesThis work was also supported by the Labex in Research on Medication and Therapeutic Innovation(LERMT)(to B.M.)and the CEA(to B.M.).
文摘The clinical efficacy of therapeutic antibodies is recognized in many indications,explaining their rapid rise in the worldwide drug market.However,therapeutic antibodies can be immunogenic by inducing a specific immune response characterized by the production of anti-drug antibodies(ADAs).ADAs can potentially increase the clearance of therapeutic antibodies,decrease their therapeutic effects1 and induce hypersensitivity reactions.Because humans are thought to be tolerant to their own proteins,sequences of the therapeutic antibodies have been humanized or human antibodies have been directly generated by technologies using human sequences.However,human(ized)antibodies exhibit highly variable levels of immunogenicity,1,2 illustrating the poor understanding of the role of sequence humanization in mitigating the immunogenicity of therapeutic antibodies.Multiple lines of evidence highlight the role of CD4 T lymphocytes during the initiation of an ADA response,3 but few T-cell epitopes of marketed therapeutic antibodies have been described to date.
