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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>These data support the PG-CAR-T cells for clinical trial of liver cancer.</p>

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MMP14 is a safe target of CAR-T therapy against liver cancer and metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月26日

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  • Ye Yu,
  • Shirui Zou,
  • Jiawei Fan,
  • Dong Yang,
  • Nan Liu,
  • Zhiyong Bai,
  • Yongjie Zhu,
  • Lihong Li,
  • Dan Cao,
  • Xudong Zhao,
  • Jiaqiong Zou

摘要

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.