Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.
Wisconsin Institute for Discovery, University of Wisconsin, Madison, WI, USA.
Biotechnol J. 2018 Feb;13(2). doi: 10.1002/biot.201700095. Epub 2017 Sep 18.
The next generation of therapeutic products to be approved for the clinic is anticipated to be cell therapies, termed "living drugs" for their capacity to dynamically and temporally respond to changes during their production ex vivo and after their administration in vivo. Genetically engineered chimeric antigen receptor (CAR) T cells have rapidly developed into powerful tools to harness the power of immune system manipulation against cancer. Regulatory agencies are beginning to approve CAR T cell therapies due to their striking efficacy in treating some hematological malignancies. However, the engineering and manufacturing of such cells remains a challenge for widespread adoption of this technology. Bioengineering approaches including biomaterials, synthetic biology, metabolic engineering, process control and automation, and in vitro disease modeling could offer promising methods to overcome some of these challenges. Here, we describe the manufacturing process of CAR T cells, highlighting potential roles for bioengineers to partner with biologists and clinicians to advance the manufacture of these complex cellular products under rigorous regulatory and quality control.
预计下一代获准进入临床应用的治疗产品将是细胞疗法,因其具有在体外生产和体内给药后动态和时间响应变化的能力,而被称为“活药物”。经过基因工程改造的嵌合抗原受体 (CAR) T 细胞已迅速发展成为利用免疫系统对抗癌症的强大工具。由于其在治疗某些血液恶性肿瘤方面的显著疗效,监管机构开始批准 CAR T 细胞疗法。然而,此类细胞的工程和制造仍然是广泛采用该技术的一个挑战。生物工程方法包括生物材料、合成生物学、代谢工程、过程控制和自动化以及体外疾病建模,可为克服其中一些挑战提供有前景的方法。在这里,我们描述了 CAR T 细胞的制造过程,强调了生物工程师与生物学家和临床医生合作的潜在作用,以在严格的监管和质量控制下推进这些复杂细胞产品的制造。