手术切除是三阴性乳腺癌（TNBC）患者的主要治疗选择，但术后局部和转移复发率较高。尽管嵌合抗原受体工程自然杀伤（CAR-NK）细胞疗法可以特异性识别和根除肿瘤细胞，但其对TNBC的治疗效力受到不利的肿瘤微环境的显着抑制，这限制了CAR-NK的浸润、存活和效应功能肿瘤块内的细胞。在此，HER1过表达TNBC靶向CAR-NK（HER1-CAR-NK）细胞采用过氧化氢酶进行基因工程改造，通过过氧化氢的催化分解，赋予它们对TNBC肿瘤内高水平氧化应激和缺氧的耐受性，是肿瘤内主要的活性氧，转化为O2。我们将这些细胞称为 HER1-CAR-CAT-NK 细胞。在使用可注射藻酸盐水凝胶进行瘤内固定后，HER1-CAR-CAT-NK 细胞能够持续减弱肿瘤缺氧，并在 TNBC 肿瘤内表现出显着增强的持久性和效应功能。因此，局部HER1-CAR-CAT-NK细胞疗法不仅抑制了局部原发性残留肿瘤的生长，而且还引发了全身抗肿瘤活性，抑制远处肿瘤的生长。这项研究强调，用过氧化氢酶对 HER1-CAR-NK 细胞进行基因工程是抑制 TNBC 肿瘤术后局部和远处复发的一种有前景的策略。

Surgical resection is a primary treatment option for triple-negative breast cancer (TNBC) patients, but it is associated with a high rate of postoperative local and metastatic relapse. Although chimeric antigen receptor-engineered natural killer (CAR-NK) cell therapy can specifically recognize and eradicate tumor cells, its therapeutic potency toward TNBCs is markedly suppressed by the hostile tumor microenvironment, which restricts the infiltration, survival and effector functions of CAR-NK cells inside the tumor masses. Herein, HER1-overexpressing TNBC-targeted CAR-NK (HER1-CAR-NK) cells were genetically engineered with catalase to endow them with tolerance toward the high levels of oxidative stress and hypoxia inside TNBC tumors through the catalytic decomposition of hydrogen peroxide, which is a principle reactive oxygen species inside tumors, into O2. We refer to these cells as HER1-CAR-CAT-NK cells. Upon intratumoral fixation with an injectable alginate hydrogel, HER1-CAR-CAT-NK cells enabled sustained tumor hypoxia attenuation and exhibited markedly enhanced persistence and effector functions inside TNBC tumors. As a result, locoregional HER1-CAR-CAT-NK cell therapy not only inhibited the growth of local primary residual tumors, but also elicited systemic antitumor activity to suppress the growth of distant tumors. This study highlights that genetic engineering of HER1-CAR-NK cells with catalase is a promising strategy to suppress the postoperative local and distant relapse of TNBC tumors.