Ben-Akiva Elana, Meyer Randall A, Wilson David R, Green Jordan J
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Adv Drug Deliv Rev. 2017 May 15;114:102-115. doi: 10.1016/j.addr.2017.05.005. Epub 2017 May 10.
The once nascent field of immunoengineering has recently blossomed to include approaches to deliver and present biomolecules to program diverse populations of lymphocytes to fight disease. Building upon improved understanding of the molecular and physical mechanics of lymphocyte activation, varied strategies for engineering surfaces to activate and deactivate T-Cells, B-Cells and natural killer cells are in preclinical and clinical development. Surfaces have been engineered at the molecular level in terms of the presence of specific biological factors, their arrangement on a surface, and their diffusivity to elicit specific lymphocyte fates. In addition, the physical and mechanical characteristics of the surface including shape, anisotropy, and rigidity of particles for lymphocyte activation have been fine-tuned. Utilizing these strategies, acellular systems have been engineered for the expansion of T-Cells and natural killer cells to clinically relevant levels for cancer therapies as well as engineered to program B-Cells to better combat infectious diseases.
免疫工程这一曾经刚起步的领域最近蓬勃发展,涵盖了递送和呈递生物分子的方法,以编程不同类型的淋巴细胞来对抗疾病。基于对淋巴细胞激活的分子和物理机制的深入理解,多种用于工程化表面以激活和失活T细胞、B细胞和自然杀伤细胞的策略正处于临床前和临床开发阶段。在分子水平上,已根据特定生物因子的存在、它们在表面的排列及其扩散性对表面进行工程化设计,以引发特定的淋巴细胞命运。此外,还对表面的物理和机械特性(包括用于淋巴细胞激活的颗粒的形状、各向异性和刚性)进行了微调。利用这些策略,已构建出无细胞系统,用于将T细胞和自然杀伤细胞扩增至临床相关水平以进行癌症治疗,同时也对B细胞进行编程以更好地对抗传染病。