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

作者：Yi Yu, Shirui Zou, Jiawei Fan, Dong Yang, Nan Liu, Zhiyong Bai, Yongjie Zhu, Lihong Li, Dan Cao, Xudong Zhao, Jiaqiong Zou · 发表于：Journal of Translational Medicine · 年份：2026 · DOI：10.1186/s12967-026-08036-x · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Immunotherapy and Immune Responses

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 b...