Purwada Alberto, Roy Krishnendu, Singh Ankur
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Acta Biomater. 2014 Apr;10(4):1728-40. doi: 10.1016/j.actbio.2013.12.036. Epub 2013 Dec 27.
Controlled modulation of immune response, especially the balance between immunostimulatory and immunosuppressive responses, is critical for a variety of clinical applications, including immunotherapies against cancer and infectious diseases, treatment of autoimmune disorders, transplant surgeries, regenerative medicine, prosthetic implants, etc. Our ability to precisely modify both innate and adaptive immune responses could provide new therapeutic directions in a variety of diseases. In the context of vaccines and immunotherapies, the interplay between antigen-presenting cells (e.g. dendritic cells and macrophages), B cells, T helper and killer subtypes, and regulatory T- and B-cell responses is critical for generating effective immunity against cancer, infectious diseases and autoimmune diseases. In recent years, immunoengineering has emerged as a new field that uses quantitative engineering tools to understand molecular-, cellular- and system-level interactions of the immune system and to develop design-driven approaches to control and modulate immune responses. Biomaterials are an integral part of this engineering toolbox and can exploit the intrinsic biological and mechanical cues of the immune system to directly modulate and train immune cells and direct their response to a particular phenotype. A large body of literature exists on strategies to evade or suppress the immune response in implants, transplantation and regenerative medicine. This review specifically focuses on the use of biomaterials for immunostimulation and controlled modulation, especially in the context of vaccines and immunotherapies against cancer, infectious diseases and autoimmune disorders. Bioengineering smart systems that can simultaneously deliver multiple bioactive agents in a controlled manner or can work as a niche for in situ priming and modulation of the immune system could significantly enhance the efficacy of next-generation immunotherapeutics. In this review, we describe our perspective on the important design aspects for the development of biomaterials that can actively modulate immune responses by stimulating receptor complexes and cells, and delivering multiple immunomodulatory biomolecules.
免疫反应的可控调节，尤其是免疫刺激和免疫抑制反应之间的平衡，对于多种临床应用至关重要，包括针对癌症和传染病的免疫疗法、自身免疫性疾病的治疗、移植手术、再生医学、假体植入等。我们精确改变先天性和适应性免疫反应的能力可为多种疾病提供新的治疗方向。在疫苗和免疫疗法的背景下，抗原呈递细胞（如树突状细胞和巨噬细胞）、B细胞、辅助性T细胞和杀伤性T细胞亚型以及调节性T细胞和B细胞反应之间的相互作用对于产生针对癌症、传染病和自身免疫性疾病的有效免疫力至关重要。近年来，免疫工程作为一个新领域应运而生，它使用定量工程工具来理解免疫系统的分子、细胞和系统水平的相互作用，并开发设计驱动的方法来控制和调节免疫反应。生物材料是这个工程工具箱的一个组成部分，可以利用免疫系统固有的生物学和机械信号来直接调节和训练免疫细胞，并引导它们对特定表型做出反应。关于在植入物、移植和再生医学中逃避或抑制免疫反应的策略，已有大量文献报道。本综述特别关注生物材料在免疫刺激和可控调节方面的应用，尤其是在针对癌症、传染病和自身免疫性疾病的疫苗和免疫疗法背景下。能够以可控方式同时递送多种生物活性剂或能够作为原位启动和调节免疫系统的微环境的生物工程智能系统，可以显著提高下一代免疫疗法的疗效。在本综述中，我们阐述了我们对于开发能够通过刺激受体复合物和细胞以及递送多种免疫调节生物分子来积极调节免疫反应的生物材料的重要设计方面的观点。
