How to Test Human CAR T Cells in Solid Tumors, the Next Frontier of CAR T Cell Therapy.
How to Test Human CAR T Cells in Solid Tumors, the Next Frontier of CAR T Cell Therapy.
复制标题
如何在实体瘤中测试人类 CAR T 细胞，这是 CAR T 细胞治疗的下一个前沿。
DOI：
10.1007/978-1-0716-3593-3_16
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Ferreira,LeonardoMR
中科院分区：
文献类型：
--
作者：
Cochrane,RussellW;Fiorentino,Andrew;Allen,Eva;Robino,RobA;Quiroga,Jaime;Ferreira,LeonardoMR
嵌合抗原受体 (CAR) T 细胞疗法已被证明是白血病和淋巴瘤的成功治疗选择。这些令人鼓舞的结果强调了过继细胞疗法在其他肿瘤学应用（即实体瘤）中的潜力。然而，CAR T 细胞尚未成功治疗实体瘤。与液体肿瘤不同，实体瘤会产生不利的肿瘤微环境（TME）。 CAR T 细胞必须运输至 TME、存活并保留其根除肿瘤的功能。然而，目前还没有通用的临床前模型来系统地测试候选 CAR 和 CAR 靶点在体内渗透和消除人类实体瘤的能力。在这里，我们提供了一个详细的方案来评估携带表达抗原的人类实体瘤的免疫缺陷 (NSG) 小鼠中的人类 CAR CD4+ 辅助 T 细胞和 CD8+ 细胞毒性 T 细胞。
Chimeric antigen receptor (CAR) T cell therapy has proven to be a successful treatment option for leukemias and lymphomas. These encouraging outcomes underscore the potential of adoptive cell therapy for other oncology applications, namely, solid tumors. However, CAR T cells are yet to succeed in treating solid tumors. Unlike liquid tumors, solid tumors create a hostile tumor microenvironment (TME). CAR T cells must traffic to the TME, survive, and retain their function to eradicate the tumor. Nevertheless, there is no universal preclinical model to systematically test candidate CARs and CAR targets for their capacity to infiltrate and eliminate human solid tumors in vivo. Here, we provide a detailed protocol to evaluate human CAR CD4+helper T cells and CD8+cytotoxic T cells in immunodeficient (NSG) mice bearing antigen-expressing human solid tumors.