The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA 30332-0313, United States; The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States.
The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States; Department of Material Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.
Adv Drug Deliv Rev. 2017 May 15;114:222-239. doi: 10.1016/j.addr.2017.06.005. Epub 2017 Jun 15.
Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies.
治疗细胞在治疗目前无法治愈的慢性疾病方面具有巨大的潜力，因为与传统的小分子药物或生物制剂相比，它们在体内具有多种综合的复杂功能。然而，由于以下两个原因，它们作为治疗产品也带来了重大挑战：（a）它们的复杂作用机制难以理解；（b）尚未开发出用于大规模、可重复生产细胞的低成本生物工艺。使用 T 细胞和树突状细胞（DC）的免疫疗法已在治疗多种类型的癌症方面显示出巨大的潜力，人类间充质基质细胞（hMSC）目前正在临床试验中作为免疫调节细胞进行广泛评估。尽管取得了这些令人兴奋的进展，但除非新的工程技术能够以经济有效的方式大规模生产高质量的治疗细胞，否则细胞治疗的全部潜力将无法实现。在这里，我们综述了以制造工艺为重点的基于细胞的免疫治疗概念，包括细胞来源、分离、扩增、修饰、质量控制（QC）和培养基要求。我们还深入探讨了当前技术如何通过新技术得到显著改进和增强，以及各学科如何汇聚以满足细胞免疫疗法大规模生产的长期需求。
