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Generation of Fcabs targeting human and murine LAG-3 as building blocks for novel bispecific antibody therapeutics
Methods ( IF 4.8 ) Pub Date : 2019-02-01 , DOI: 10.1016/j.ymeth.2018.09.003
Katy L. Everett , Matthew Kraman , Francisca P.G. Wollerton , Carlo Zimarino , Katarzyna Kmiecik , Miguel Gaspar , Sarka Pechouckova , Natalie L. Allen , Jacqueline F. Doody , Mihriban Tuna

The immunoglobulin superfamily protein lymphocyte-activation gene 3 (LAG-3) participates in immune suppression and has been identified as a suitable target for cancer therapies. In order to generate bispecific antibodies targeting LAG-3, Fcabs (Fc-region with antigen binding) targeting human and murine LAG-3 were generated from phage libraries. These Fcabs bind to LAG-3, inhibiting its interaction with MHC class II, and induce IL-2 production in a T cell assay. Bispecific antibodies, known as mAb2, were produced by replacing the Fc region of a monoclonal antibody with Fcab sequences in the CH3 domain. mAb2 containing anti-LAG-3 Fcabs have mAb-like biophysical characteristics and retain LAG-3 binding and functional activity. mAb2 can thus be generated using multiple Fabs to investigate bispecific parings and develop novel therapeutics.

中文翻译:

生成靶向人和鼠 LAG-3 作为新型双特异性抗体疗法构建模块的 Fcab

免疫球蛋白超家族蛋白淋巴细胞激活基因 3 (LAG-3) 参与免疫抑制,已被确定为癌症治疗的合适靶点。为了生成靶向 LAG-3 的双特异性抗体,从噬菌体文库生成靶向人和鼠 LAG-3 的 Fcab(具有抗原结合的 Fc 区)。这些 Fcab 与 LAG-3 结合,抑制其与 MHC II 类的相互作用,并在 T 细胞试验中诱导 IL-2 的产生。双特异性抗体,称为 mAb2,是通过用 CH3 结构域中的 Fcab 序列替换单克隆抗体的 Fc 区产生的。含有抗 LAG-3 Fcab 的 mAb2 具有类似 mAb 的生物物理特性,并保留 LAG-3 结合和功能活性。因此可以使用多个 Fab 生成 mAb2,以研究双特异性配对并开发新的治疗方法。
更新日期:2019-02-01
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