Humanized and fully human sequence-derived therapeutic antibodies retain the capacity to induce anti-drug antibodies. Daclizumab (humanized version of the murine anti-Tac antibody; E.HAT) was selected for a proof of concept application of engineering approaches to reduce potential immunogenicity due to its demonstrated immunogenicity in the clinic. Reduced immunogenicity variants of E.HAT were created by identifying and modifying a CD4+ T cell epitope region in the VH region. Variant epitope region peptides were selected for their reduced capacity to induce CD4+ T cell proliferative responses in vitro. Variant antibody molecules were created, and CD25 affinity and potency were similar to the unmodified parent antibody. Fab fragments from the variant antibodies induced a lower frequency and magnitude of responses in human peripheral blood mononuclear cells proliferation tests. By the empirical selection of two amino acid mutations, fully functional humanized E.HAT antibodies with reduced potential to induce immune responses in vitro were created.

中文翻译：

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保留功能活性的降低免疫原性的人源化抗CD25单克隆抗体的设计，创建和体外测试。

人源化和完全人源于序列的治疗性抗体保留了诱导抗药物抗体的能力。选择达克珠单抗（鼠源抗Tac抗体的人源化版本； E.HAT），以证明其工程手段可降低潜在的免疫原性的概念性应用在临床上得到了证明，从而可降低其潜在的免疫原性。通过鉴定和修饰VH区中的CD4 + T细胞表位区，可以降低E.HAT的免疫原性。选择变异的抗原决定簇区域肽以降低其诱导体外CD4 + T细胞增殖反应的能力。创建了变异抗体分子，并且CD25亲和力和效价与未修饰的亲本抗体相似。来自变异抗体的Fab片段在人外周血单核细胞增殖测试中诱导了较低的响应频率和幅度。通过两个氨基酸突变的经验选择，创建了具有降低体外诱导免疫反应潜能的全功能人源化E.HAT抗体。