| Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis |
| Sun, B; Guo, J; Yang, D; Hu, QC; Ma, HY; Tian, PW; Liu, N; Lv, LB; Yan, LZ; Ding, H; Fu, MY; Gou, HF; Cao, D; Liu, D; Shi, P ; Chen, NY; Li, WM; Zhao, XD
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| 2026
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| 发表期刊 | Oncogene
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| ISSN | 0950-9232
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| 卷号 | 45期号:21页码:2058-2070 |
| 摘要 | Utilizing CAR-T cells to eliminate circulating tumor cells (CTCs) and inhibit metastasis is a promising strategy. However, this approach is hindered by the lack of specific antigens. Membrane-bound HSP70 (mHSP70) is commonly expressed on the cell membrane of numerous tumor types, notably on CTCs, making it an ideal target for CAR-T therapy to treat these malignancies and prevent metastasis. Here, we generated CAR T cells based on natural ligand granzyme B (GrB-CAR T) targeting mHSP70. GrB-CAR T cells exhibited potent cytotoxicity against a broad spectrum of cancer cell lines and stem-like cancer cells in vitro and effectively inhibited xenograft tumor growth in vivo. Importantly, CTCs maintain mHSP70 expression in xenograft models, and GrB-CAR T cells markedly decreased the number of CTCs, thereby preventing cancer metastasis. Moreover, despite human granzyme B exhibits cross-reactivity with mouse and macaque mHSP70-particularly given the complete homology between macaque and human mHSP70-no obvious adverse effects were observed in the animals treated with GrB-CAR T cells. These results demonstrate GrB-CAR T cells as a safe and effective approach with broad-spectrum anticancer activity and provide compelling experimental evidence for CAR T cell-mediated metastasis inhibition through targeting CTCs. |
| 收录类别 | SCIE
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14854
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| 专题 | 科研部门_进化与功能基因组学（施鹏）
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推荐引用方式
GB/T 7714 |
Sun, B,Guo, J,Yang, D,et al. Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis[J]. Oncogene,2026,45(21):2058-2070.
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| APA |
Sun, B.,Guo, J.,Yang, D.,Hu, QC.,Ma, HY.,...&Zhao, XD.(2026).Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis.Oncogene,45(21),2058-2070.
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| MLA |
Sun, B,et al."Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis".Oncogene 45.21(2026):2058-2070.
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