SLC7A11-specific CAR-T cell therapy potently targets colorectal and pancreatic cancer

SLC7A11特异性CAR-T细胞疗法可有效靶向结直肠癌和胰腺癌。

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作者:Xiaoxue Pan ,Jichang Li ,Jing Zhu ,Xin Wang ,Yucun Liu ,Xiaodong Tian ,Yinmo Yang ,Pengyuan Wang ,Shanwen Chen

Abstract

SLC7A11 is highly expressed in various solid tumors, including colorectal cancer and pancreatic cancer. The aim of the study was to report the therapeutic potential of SLC7A11 CAR-T therapy. The SLC7A11-specific antibodies were generated by hybridoma and humanization technologies. The cytotoxicity was validated in vitro through co-culture assays of effector cells with cancer cell lines. The anti-tumor studies in vivo were evaluated by cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. We first confirmed the tumor specificity of SLC7A11 and then successfully developed SLC7A11-specific CAR-T cells. CCK-8 and LDH cytotoxicity assays demonstrated that cancer cells co-cultured with CAR-T cells exhibited higher mortality rates. Animal experiments showed that SLC7A11 CAR-T treatment suppressed the tumor growth without causing significant abnormalities in blood biochemical parameters. In conclusion, SLC7A11 CAR-T cell therapy showed remarkable anti-tumor capabilities and safety in colorectal and pancreatic cancer.

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