Abstract Objectives Traditional cancer therapy and regular immunotherapy are ineffective for treating triple‐negative breast cancer (TNBC) patients. Recently, chimeric antigen receptor‐engineered natural killer cells (CAR NK) have been applied to target several hormone receptors on different cancer cells to improve the efficacy of immunotherapy. Furthermore, epidermal growth factor receptor (EGFR) is a potential therapeutic target for TNBC. Here, we demonstrated that EGFR‐specific CAR NK cells (EGFR‐CAR NK cells) could be potentially used to treat patients with TNBC exhibiting enhanced EGFR expression. Materials and methods We investigated the cytotoxic effects of EGFR‐CAR NK cells against TNBC cells in vitro and in vivo. The two types of EGFR‐CAR NK cells were generated by transducing lentiviral vectors containing DNA sequences encoding the single‐chain variable fragment (scFv) regions of the two anti‐EGFR antibodies. The cytotoxic and anti‐tumor effects of the two cell types were examined by performing cytokine release and cytotoxicity assays in vitro, and tumor growth assays in breast cancer cell line‐derived xenograft (CLDX) and patient‐derived xenograft (PDX) mouse models. Results Both EGFR‐CAR NK cell types were activated by TNBC cells exhibiting upregulated EGFR expression and specifically triggered the lysis of the TNBC cells in vitro. Furthermore, the two EGFR‐CAR NK cell types inhibited CLDX and PDX tumors in mice. Conclusions This study suggested that treatment with EGFR‐CAR NK cells could be a promising strategy for TNBC patients.

中文翻译：

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通过表达特定嵌合抗原受体的自然杀伤细胞靶向表皮生长因子过度表达的三阴性乳腺癌


摘要 目的传统癌症治疗和常规免疫治疗对于治疗三阴性乳腺癌（TNBC）患者无效。最近，嵌合抗原受体工程自然杀伤细胞（CAR NK）已被应用于靶向不同癌细胞上的多种激素受体，以提高免疫治疗的疗效。此外，表皮生长因子受体（EGFR）是TNBC的潜在治疗靶点。在这里，我们证明了 EGFR 特异性 CAR NK 细胞（EGFR-CAR NK 细胞）有可能用于治疗 EGFR 表达增强的 TNBC 患者。材料和方法我们在体外和体内研究了 EGFR-CAR NK 细胞对 TNBC 细胞的细胞毒性作用。这两种类型的 EGFR-CAR NK 细胞是通过转导含有编码两种抗 EGFR 抗体的单链可变片段 (scFv) 区域的 DNA 序列的慢病毒载体而产生的。通过体外细胞因子释放和细胞毒性测定以及乳腺癌细胞系来源的异种移植物（CLDX）和患者来源的异种移植物（PDX）小鼠模型中的肿瘤生长测定，检查了两种细胞类型的细胞毒性和抗肿瘤作用。结果 两种 EGFR-CAR NK 细胞类型均被表现出上调 EGFR 表达的 TNBC 细胞激活，并在体外特异性触发 TNBC 细胞裂解。此外，两种 EGFR-CAR NK 细胞类型可抑制小鼠体内的 CLDX 和 PDX 肿瘤。结论 这项研究表明，EGFR-CAR NK 细胞治疗可能是 TNBC 患者的一种有前途的策略。