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Engineering Functional Particles to Modulate T Cell Responses
Accounts of Materials Research ( IF 14.0 ) Pub Date : 2024-07-18 , DOI: 10.1021/accountsmr.4c00105 Yudong Li 1 , Shukun Li 1, 2 , Jari F. Scheerstra 1 , Tania Patiño 1 , Jan C. M. van Hest 1 , Loai K. E. A. Abdelmohsen 1
Accounts of Materials Research ( IF 14.0 ) Pub Date : 2024-07-18 , DOI: 10.1021/accountsmr.4c00105 Yudong Li 1 , Shukun Li 1, 2 , Jari F. Scheerstra 1 , Tania Patiño 1 , Jan C. M. van Hest 1 , Loai K. E. A. Abdelmohsen 1
Affiliation
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T cells play a critical role in adaptive immune responses. They work with other immune cells such as B cells to protect our bodies when the first line of defense, the innate immune system, is overcome by certain infectious diseases or cancers. Studying and regulating the responses of T cells, such as activation, proliferation, and differentiation, helps us understand not only their behavior in vivo but also their translation and application in the field of immunotherapy, such as adoptive T cell therapy and immune checkpoint therapy, the situations in which T cells cannot fight cancer alone and require external engineering regulation to help them. Nano- to micrometer-sized particulate biomaterials have achieved great progress in the assistance of T cell-based immunomodulation. For example, various types of microparticles decorated with T cell recognition and activation signals to mimic native antigen-presenting cells have shown successful ex vivo expansion of primary T cells and have been approved for clinical use in adoptive T cell therapy. Functional particles can also serve as vehicles for transporting cargos including small molecule drugs, cytokines, and antibodies. Especially for cargos with limited bioavailability and high repeat-dose toxicity, systemic administration in their free form is difficult. By using particle-assisted systems, the delivery can be tailored on demand, of which targeting and controlled release are two typical examples, ultimately aiding in the regulation of T cell responses. Furthermore, when T cells become overactive and behave in ways that contradict our expectations, such as attacking our own cells or innocuous foreign molecules, this can lead to a breakdown of immune tolerance. In such cases, particles to help reprogram those overactive T cells or suppress their activity are appreciated in vivo. The urgent need to introduce immune stimulation into the treatment of cancers, infectious diseases, and autoimmune diseases has driven recent advances in the engineering of functional particulate biomaterials that regulate T cell responses. In this Account, we will first cover a brief overview of the process of T cell-based immunomodulation from principle to development. It then outlines critical points in the design of functional particle platforms, including materials, size, morphology, surface engineering, and delivery of cargos, to modulate the features of T cells, and introduces selected work from our and other research groups with a focus on three major therapeutic applications: adoptive T cell therapy, immune checkpoint therapy, and immune tolerance restoration. Current challenges and future opportunities are also discussed.
中文翻译：
设计功能颗粒以调节 T 细胞反应
T 细胞在适应性免疫反应中起关键作用。它们与其他免疫细胞（如 B 细胞）一起工作，在第一道防线（先天免疫系统）被某些传染病或癌症克服时保护我们的身体。研究和调节 T 细胞的反应，如活化、增殖和分化，不仅有助于我们了解它们在体内的行为，还有助于我们了解它们在免疫治疗领域的转化和应用，例如过继性 T 细胞治疗和免疫检查点治疗，T 细胞无法单独对抗癌症，需要外部工程调节来帮助它们的情况。纳米至微米大小的颗粒生物材料在基于 T 细胞的免疫调节辅助方面取得了巨大进展。例如，用 T 细胞识别和激活信号修饰以模拟天然抗原呈递细胞的各种类型的微粒已显示出原代 T 细胞的成功离体扩增，并已获准用于过继性 T 细胞疗法。功能性颗粒还可以用作运输货物的载体，包括小分子药物、细胞因子和抗体。特别是对于生物利用度有限且重复剂量毒性高的货物，游离形式的全身给药是困难的。通过使用粒子辅助系统，可以按需定制递送，其中靶向和控释是两个典型的例子，最终有助于调节 T 细胞反应。此外，当 T 细胞变得过度活跃并以与我们的预期相悖的方式行为时，例如攻击我们自己的细胞或无害的外来分子，这可能会导致免疫耐受的崩溃。 在这种情况下，有助于重新编程那些过度活跃的 T 细胞或抑制其活性的颗粒在体内受到赞赏。迫切需要将免疫刺激引入癌症、传染病和自身免疫性疾病的治疗中，这推动了调节 T 细胞反应的功能性颗粒生物材料工程的最新进展。在本账户中，我们将首先简要概述基于 T 细胞的免疫调节从原理到发展的过程。然后，它概述了功能颗粒平台设计中的关键点，包括材料、尺寸、形态、表面工程和货物交付，以调节 T 细胞的特性，并介绍了我们和其他研究小组的精选工作，重点关注三个主要治疗应用：过继性 T 细胞疗法、免疫检查点疗法和免疫耐受恢复。还讨论了当前的挑战和未来的机遇。
更新日期：2024-07-18
中文翻译：
设计功能颗粒以调节 T 细胞反应
T 细胞在适应性免疫反应中起关键作用。它们与其他免疫细胞（如 B 细胞）一起工作，在第一道防线（先天免疫系统）被某些传染病或癌症克服时保护我们的身体。研究和调节 T 细胞的反应，如活化、增殖和分化，不仅有助于我们了解它们在体内的行为，还有助于我们了解它们在免疫治疗领域的转化和应用，例如过继性 T 细胞治疗和免疫检查点治疗，T 细胞无法单独对抗癌症，需要外部工程调节来帮助它们的情况。纳米至微米大小的颗粒生物材料在基于 T 细胞的免疫调节辅助方面取得了巨大进展。例如，用 T 细胞识别和激活信号修饰以模拟天然抗原呈递细胞的各种类型的微粒已显示出原代 T 细胞的成功离体扩增，并已获准用于过继性 T 细胞疗法。功能性颗粒还可以用作运输货物的载体，包括小分子药物、细胞因子和抗体。特别是对于生物利用度有限且重复剂量毒性高的货物，游离形式的全身给药是困难的。通过使用粒子辅助系统，可以按需定制递送，其中靶向和控释是两个典型的例子，最终有助于调节 T 细胞反应。此外，当 T 细胞变得过度活跃并以与我们的预期相悖的方式行为时，例如攻击我们自己的细胞或无害的外来分子，这可能会导致免疫耐受的崩溃。 在这种情况下，有助于重新编程那些过度活跃的 T 细胞或抑制其活性的颗粒在体内受到赞赏。迫切需要将免疫刺激引入癌症、传染病和自身免疫性疾病的治疗中，这推动了调节 T 细胞反应的功能性颗粒生物材料工程的最新进展。在本账户中，我们将首先简要概述基于 T 细胞的免疫调节从原理到发展的过程。然后，它概述了功能颗粒平台设计中的关键点，包括材料、尺寸、形态、表面工程和货物交付，以调节 T 细胞的特性，并介绍了我们和其他研究小组的精选工作，重点关注三个主要治疗应用：过继性 T 细胞疗法、免疫检查点疗法和免疫耐受恢复。还讨论了当前的挑战和未来的机遇。
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