Journal of translational medicine · 2026
MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yu Ye, Zou Shirui, Fan Jiawei, Yang Dong, Liu Nan, Bai Zhiyong, Zhu Yongjie, Li Lihong, Cao Dan, Zhao Xudong, Zou Jiaqiong
Аннотация
BACKGROUND: Hepatocellular 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.
METHODS: Here, 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.
RESULTS: PG-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.
CONCLUSION: These data support the PG-CAR-T cells for clinical trial of liver cancer.
METHODS: Here, 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.
RESULTS: PG-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.
CONCLUSION: These data support the PG-CAR-T cells for clinical trial of liver cancer.