Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions

IF 4.9 3区 医学 Q2 IMMUNOLOGY Immunology Pub Date : 2024-07-01 DOI:10.1111/imm.13828
Marianne Strazza, Ruijiang Song, Shannon Hiner, Adam Mor
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Abstract

Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.

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改变蛋白质在细胞表面的位置是一种很有前景的调节 T 细胞功能的策略。
靶向 T 细胞上的免疫受体是治疗癌症和自身免疫病的常用策略。通常,这是通过靶向刺激性或抑制性共受体配体结合位点的单克隆抗体来实现的。阻断配体结合可防止下游信号传导并调节特定的 T 细胞功能。自 1985 年以来,美国食品和药物管理局已批准了 100 多种针对免疫受体的单克隆抗体。这种治疗方法大大改善了对多种免疫相关疾病患者的治疗;然而,许多患者并无反应,一些患者还出现了免疫相关不良反应。原因之一是没有考虑到这些受体在免疫突触背景下在免疫细胞细胞表面的定位。除了阻断配体结合外,改变这些受体在免疫突触不同区块中细胞表面的位置也可作为治疗这些患者的一种高效、安全的替代方法。本综述讨论了改变蛋白质在免疫突触内定位的潜在治疗优势,并总结了该领域已发表的研究成果。它还讨论了使用双特异性抗体诱导细胞表面受体聚集的新方法。它介绍了针对细胞表面信号受体复合物组织开发新型抗体的原理。这种方法为治疗对当前免疫疗法有抗药性的癌症患者提供了一种创新的新兴技术。
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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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