Research advances of monitoring and tracking chimeric antigen receptor T cell in vivo
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Abstract: Chimeric antigen receptor T cells(CAR-T) therapy, in which T cells are genetically engineered to specifically recognize and kill targeted tumor cells, has been shown to be remarkably effective in the treatment of some refractory/recurrent leukemia and lymphoma. However, monitoring the migration and survival of CAR-T cells as well as quantifying their number and durability in vivo need further study, so that to determine their biodistribution of vital organs and tissues. A series of imaging techniques, enabling noninvasively continuous localization and dynamic tracking of cells infused in vivo, have provided us with ideas. This review summarizes several in vivo CAR-T cell trafficking techniques, which are expected to provide guidance for CAR-T therapy in clinical practice.
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Key words:
- CAR-T cell /
- cell labeling /
- noninvasive tracking /
- dynamic monitoring
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表 1 常见的报告基因及探针
报告基因 成像探针 显像模式 CAR-T靶点 验证模型 参考文献 HSV1-tk 18F-FHBG PET IL-13 zatakine 临床研究 [11-12] HSV1-sr39tk 18F-FHBG PET B7H3 小鼠骨肉瘤异种移植模型 [13] eDFHRhSSTR2 18F-TMP68Ga-DOTATOC PETPET GD2ICAM-1 小鼠骨肉瘤异种移植模型小鼠未分化甲状腺癌异种移植模型 [14][15] hPSMADAbR1 18F-DCFPyL86Y/177Lu-AABD PETPET/SPECT CD19CD19 小鼠急性淋巴细胞白血病异种移植模型小鼠急性淋巴细胞白血病皮下瘤异种移植模型 [16][17] hNIS 99mTcO4-18F-BF4-/99mTcO4- SPECTPET/SPECT PMSAPan-ErbB 小鼠前列腺癌异种移植模型小鼠乳腺癌异种移植模型 [18][19] 表 2 常见的直接标记及显像探针
成像探针 标记方式 显像模式 CAR-T靶点 验证模型 参考文献 111In-羟喹啉 共孵育 SPECT HER2 临床研究 [27] 89Zr-DFO 共孵育 PET CD19 小鼠淋巴瘤异种移植模型 [28] 89Zr-羟喹啉 共孵育 PET IL-13Rα2和PSCA 小鼠胶质母细胞瘤和前列腺癌异种移植模型 [29] 89Zr-二氧化硅纳米标签 鱼精蛋白和肝素促入胞 PET/NIRF hCEA 小鼠腹腔卵巢癌异种移植模型 [30] 68Ga-羟喹啉 共孵育 PET CD19 小鼠伯基特淋巴瘤血液瘤模型及CD19(+)K562皮下瘤异种移植模型 [31] 64Cu-AuNPs 电穿孔 PET CD19 正常小鼠 [32] 89Zr-DFO-ICOS单抗 抗原-抗体结合 PET mCD19 鼠源性淋巴瘤模型 [33] PFC 共孵育 MRI EGFRvⅢ 小鼠胶质母细胞瘤异种移植模型 [34] TAT-PFC纳米乳剂 细胞穿膜肽引导入胞 MRI EGFRvⅢ 小鼠胶质母细胞瘤异种移植模型 [35] USPIO PLL中和作用促进内吞 MRI EGFRvⅢ 小鼠胶质母细胞瘤异种移植模型 [36] -
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