Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Front Immunol. 2021 Feb 18;11:624568. doi: 10.3389/fimmu.2020.624568. eCollection 2020.
Type 1 diabetes (T1D) is widely considered to be a T cell driven autoimmune disease resulting in reduced insulin production due to dysfunction/destruction of pancreatic β cells. Currently, there continues to be a need for immunotherapies that selectively reestablish persistent β cell-specific self-tolerance for the prevention and remission of T1D in the clinic. The utilization of monoclonal antibodies (mAb) is one strategy to target specific immune cell populations inducing autoimmune-driven pathology. Several mAb have proven to be clinically safe and exhibit varying degrees of efficacy in modulating autoimmunity, including T1D. Traditionally, mAb therapies have been used to deplete a targeted cell population regardless of antigenic specificity. However, this treatment strategy can prove detrimental resulting in the loss of acquired protective immunity. Nondepleting mAb have also been applied to modulate the function of immune effector cells. Recent studies have begun to define novel mechanisms associated with mAb-based immunotherapy that alter the function of targeted effector cell pools. These results suggest short course mAb therapies may have persistent effects for regaining and maintaining self-tolerance. Furthermore, the flexibility to manipulate mAb properties permits the development of novel strategies to target multiple antigens and/or deliver therapeutic drugs by a single mAb molecule. Here, we discuss current and potential future therapeutic mAb treatment strategies for T1D, and T cell-mediated autoimmunity.
1 型糖尿病（T1D）被广泛认为是一种 T 细胞驱动的自身免疫性疾病，由于胰腺β细胞的功能障碍/破坏，导致胰岛素产生减少。目前，临床上仍然需要免疫疗法，以选择性地重新建立持续的β细胞特异性自身耐受，从而预防和缓解 T1D。单克隆抗体（mAb）的利用是一种靶向特定免疫细胞群的策略，可诱导自身免疫驱动的病理。一些 mAb 已被证明在临床上是安全的，并在调节自身免疫方面表现出不同程度的疗效，包括 T1D。传统上，mAb 疗法被用于耗尽靶向细胞群，而不管其抗原特异性如何。然而，这种治疗策略可能会产生有害影响，导致获得性保护性免疫的丧失。非耗竭性 mAb 也被应用于调节免疫效应细胞的功能。最近的研究开始定义与 mAb 为基础的免疫疗法相关的新机制，这些机制改变了靶向效应细胞池的功能。这些结果表明，短期 mAb 治疗可能具有持久的效果，可恢复和维持自身耐受。此外，操纵 mAb 特性的灵活性允许开发新的策略，以靶向多个抗原和/或通过单个 mAb 分子输送治疗药物。在这里，我们讨论当前和潜在的未来 T1D 和 T 细胞介导的自身免疫的治疗性 mAb 治疗策略。
