Mangal Joslyn L, Handlos Jamie L, Esrafili Arezoo, Inamdar Sahil, Mcmillian Sidnee, Wankhede Mamta, Gottardi Riccardo, Acharya Abhinav P
Biological Design Graduate Program, School for Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
Department of Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85281, USA.
Cancers (Basel). 2021 Mar 5;13(5):1123. doi: 10.3390/cancers13051123.
Chimeric antigen receptor (CAR) T cell-based therapies have shown tremendous advancement in clinical and pre-clinical studies for the treatment of hematological malignancies, such as the refractory of pre-B cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and large B cell lymphoma (LBCL). However, CAR T cell therapy for solid tumors has not been successful clinically. Although, some research efforts, such as combining CARs with immune checkpoint inhibitor-based therapy, have been used to expand the application of CAR T cells for the treatment of solid tumors. Importantly, further understanding of the coordination of nutrient and energy supplies needed for CAR T cell expansion and function, especially in the tumor microenvironment (TME), is greatly needed. In addition to CAR T cells, there is great interest in utilizing other types of CAR immune cells, such as CAR NK and CAR macrophages that can infiltrate solid tumors. However, the metabolic competition in the TME between cancer cells and immune cells remains a challenge. Bioengineering technologies, such as metabolic engineering, can make a substantial contribution when developing CAR cells to have an ability to overcome nutrient-paucity in the solid TME. This review introduces technologies that have been used to generate metabolically fit CAR-immune cells as a treatment for hematological malignancies and solid tumors, and briefly discusses the challenges to treat solid tumors with CAR-immune cells.
嵌合抗原受体（CAR）T细胞疗法在血液系统恶性肿瘤的临床和临床前研究中取得了巨大进展，如前B细胞急性淋巴细胞白血病（B-ALL）、慢性淋巴细胞白血病（CLL）和大B细胞淋巴瘤（LBCL）的难治性病例。然而，CAR T细胞疗法在实体瘤治疗方面尚未在临床上取得成功。尽管如此，一些研究工作，如将CAR与基于免疫检查点抑制剂的疗法相结合，已被用于扩大CAR T细胞在实体瘤治疗中的应用。重要的是，迫切需要进一步了解CAR T细胞扩增和功能所需的营养和能量供应的协调情况，尤其是在肿瘤微环境（TME）中。除了CAR T细胞外，人们对利用其他类型的CAR免疫细胞也很感兴趣，如能够浸润实体瘤的CAR NK细胞和CAR巨噬细胞。然而，癌细胞与免疫细胞在TME中的代谢竞争仍然是一个挑战。生物工程技术，如代谢工程，在开发具有克服实体TME中营养缺乏能力的CAR细胞时可以做出重大贡献。本综述介绍了用于生成代谢适应的CAR免疫细胞以治疗血液系统恶性肿瘤和实体瘤的技术，并简要讨论了用CAR免疫细胞治疗实体瘤所面临的挑战。
