MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis
Yu, Y; Zou, SR; Fan, JW; Yang, D; Liu, N; Bai, ZY; Zhu, YJ; Li, LH; Cao, D; Zhao, XD; Zou, JQ
2026
发表期刊J. Transl. Med.
卷号24期号:1
摘要BackgroundHepatocellular carcinoma (HCC) is one of the most lethal tumors, and effective treatments for HCC, especially metastatic HCC, are lacking. Chimeric antigen receptor (CAR)-T-cell therapy is considered a promising development in cancer treatment, but to date, CAR-T-cell therapy for solid tumors remains limited. Matrix metalloproteinase 14 (MMP14), the only membrane-bound collagenase, is highly expressed in HCC and other solid tumors and plays critical roles in invasion and metastasis.MethodsHere, we aimed to determine whether CAR-T cells targeting MMP14 could effectively treat HCC. CAR-T cells were designed with peptide G (PG) to specifically recognize MMP14. These cells were evaluated for their cancer-killing efficacy in vitro under MMP14-dependent conditions and tested for antitumor activity in a subcutaneous xenograft liver cancer model. Additionally, a spontaneous liver cancer metastasis model was employed to assess the impact of PG-CAR-T cells on metastasis suppression through circulating tumor cells (CTCs) elimination. The safety profile of PG-CAR-T cells was further investigated in both murine and nonhuman primate models.ResultsPG-CAR-T cells demonstrated efficient MMP14-dependent killing of cancer cells in vitro and exhibited antitumor effects in the subcutaneous xenograft liver cancer model. In the metastasis model, PG-CAR-T cells significantly inhibited metastasis by eliminating CTCs. Furthermore, PG-CAR-T cells showed a favorable safety profile in both mice and nonhuman primates.ConclusionThese data support the PG-CAR-T cells for clinical trial of liver cancer.
收录类别SCIE
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/15122
专题管理、支撑部门_高等级生物安全灵长类动物实验中心(P3)
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Yu, Y,Zou, SR,Fan, JW,et al. MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis[J]. J. Transl. Med.,2026,24(1).
APA Yu, Y.,Zou, SR.,Fan, JW.,Yang, D.,Liu, N.,...&Zou, JQ.(2026).MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis.J. Transl. Med.,24(1).
MLA Yu, Y,et al."MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis".J. Transl. Med. 24.1(2026).
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