Department of Pathology, Immunology Division, University of Cambridge, Cambridge, UK.
Centre for Rheumatology, Division of Medicine, University College London, London, UK.
Trends Immunol. 2017 Dec;38(12):916-926. doi: 10.1016/j.it.2017.07.005. Epub 2017 Aug 11.
Therapeutic antibodies targeting disease-associated antigens are key tools in the treatment of cancer and autoimmunity. So far, therapeutic antibodies have targeted antigens that are, or are presumed to be, extracellular. A largely overlooked property of antibodies is their functional activity inside cells. The diverse literature dealing with intracellular antibodies emerged historically from studies of the properties of some autoantibodies. The identification of tripartite motif (TRIM) 21 as an intracellular Fc receptor linking cytosolic antibody recognition to the ubiquitin proteasome system brings this research into sharper focus. We review critically the research related to intracellular antibodies, link this to the TRIM21 effector mechanism, and highlight how this work is exposing the previously restricted intracellular space to the potential of therapeutic antibodies.
针对疾病相关抗原的治疗性抗体是癌症和自身免疫治疗的关键工具。到目前为止，治疗性抗体已经针对那些被认为是细胞外的抗原。抗体的一个很大程度上被忽视的特性是它们在细胞内的功能活性。与细胞内抗体有关的多样化文献历史上源于对某些自身抗体特性的研究。三基序蛋白 21（TRIM21）作为一种细胞内 Fc 受体，将细胞质内抗体识别与泛素蛋白酶体系统联系起来，使这项研究更加引人注目。我们批判性地回顾了与细胞内抗体相关的研究，将其与 TRIM21 效应机制联系起来，并强调了这项工作如何将以前受到限制的细胞内空间暴露于治疗性抗体的潜在可能性。
