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Anti CD4 antibodies to prevent in particular graft-versus-host-disease (GVHD)

机译:抗CD4抗体可特别预防移植物抗宿主病(GVHD)

摘要

The present invention relates to, among others, an in vitro method of modifying a cell graft containing immune cells comprising the steps of incubating a cell graft containing immune cells with an anti CD4 antibody wherein said incubating is carried out for from 1 minute to 7 days, b) removing unbound antibody from said graft; as well as to corresponding modified grafts and uses. The invention further relates to the modification of antibodies reactive to the CD4 human leukocyte antigen to provide anti-CD4 antibodies that have a reduced number of potential T-cell epitopes but retain the ability to bind to CD4, such as to an anti human CD4-antibody comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein at least one T cell epitope located outside the CDRs of said immunoglobulin variable domains is removed from said immunoglobulin variable domains. Preferably, the specificity and mode of action of the anti-CD4 antibodies are not affected by the modification(s).
机译:本发明尤其涉及修饰包含免疫细胞的细胞移植物的体外方法,其包括将包含免疫细胞的细胞移植物与抗CD4抗体一起温育的步骤,其中所述温育进行1分钟至7天。 b)从所述移植物中去除未结合的抗体;以及相应的改良嫁接物和用途。本发明进一步涉及对与CD4人白细胞抗原具有反应性的抗体的修饰,以提供具有减少数量的潜在T细胞表位但保留与CD4结合的能力的抗CD4抗体,例如与抗人CD4结合的能力。包含重链免疫球蛋白可变域(VH)和轻链免疫球蛋白可变域(VL)的抗体,其中至少一个位于所述免疫球蛋白可变域的CDR之外的T细胞表位从所述免疫球蛋白可变域中去除。优选地,抗CD4抗体的特异性和作用方式不受修饰的影响。

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