Masaryk University Brno, Faculty of Medicine, Department of Histology and Embryology, Kamenice 5, Brno 62500, Czech Republic.
St. Anne's University Hospital Brno, International Clinical Research Center, Pekarska 53, Brno 656 91, Czech Republic.
J Immunol Res. 2021 Mar 27;2021:6644685. doi: 10.1155/2021/6644685. eCollection 2021.
Chimeric antigen receptor T-cells (CAR T-cells) represent a novel and promising approach in cancer immunotherapy. According to the World Health Organization (WHO), the number of oncological patients is steadily growing in developed countries despite immense progress in oncological treatments, and the prognosis of individual patients is still relatively poor. Exceptional results have been recorded for CAR T-cell therapy in patients suffering from B-cell malignancies. This success opens up the possibility of using the same approach for other types of cancers. To date, the most common method for CAR T-cell generation is the use of viral vectors. However, dealing with virus-derived vectors brings possible obstacles in the CAR T-cell manufacturing process owing to strict regulations and high cost demands. Alternative approaches may facilitate further development and the transfer of the method to clinical practice. The most promising substitutes for virus-derived vectors are transposon-derived vectors, most commonly sleeping beauty, which offer great coding capability and a safe integration profile while maintaining a relatively low production cost. This review is aimed at summarizing the state of the art of nonviral approaches in CAR T-cell generation, with a unique perspective on the conditions in clinical applications and current Good Manufacturing Practice. If CAR T-cell therapy is to be routinely used in medical practice, the manufacturing cost and complexity need to be as low as possible, and transposon-based vectors seem to meet these criteria better than viral-based vectors.
嵌合抗原受体 T 细胞（CAR T 细胞）在癌症免疫疗法中代表了一种新颖且有前途的方法。根据世界卫生组织（WHO）的数据，尽管在癌症治疗方面取得了巨大进展，但发达国家的癌症患者数量仍在稳步增加，个别患者的预后仍然相对较差。CAR T 细胞疗法在治疗 B 细胞恶性肿瘤患者方面取得了非凡的效果。这一成功为其他类型的癌症使用相同的方法开辟了可能性。迄今为止，CAR T 细胞生成最常见的方法是使用病毒载体。然而，由于严格的规定和高成本要求，处理源自病毒的载体会给 CAR T 细胞制造过程带来可能的障碍。替代方法可能会促进进一步的发展并将该方法转移到临床实践中。源自病毒的载体最有前途的替代品是转座子衍生的载体，最常见的是睡美人，它提供了出色的编码能力和安全的整合谱，同时保持相对较低的生产成本。本综述旨在总结 CAR T 细胞生成中非病毒方法的最新进展，特别关注临床应用和现行良好生产规范的条件。如果要将 CAR T 细胞疗法常规用于医学实践，则制造的成本和复杂性需要尽可能低，而基于转座子的载体似乎比基于病毒的载体更能满足这些标准。
