Chen Minhua, Li Yutong, Wu Yu, Xie Siqi, Ma Jie, Yue Jingjing, Lv Rong, Tian Zhigang, Fang Fang, Xiao Weihua
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Cancers (Basel). 2021 Nov 22;13(22):5866. doi: 10.3390/cancers13225866.
Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 10 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.
自然杀伤(NK)细胞因其泛特异性的靶标识别能力,在多种癌症的治疗中展现出巨大的治疗潜力。众多报告表明,NK细胞免疫疗法是治疗血液系统恶性肿瘤的有效治疗方法,但对实体瘤的疗效有限。在本研究中,使用了几种卵巢癌(OC)模型来测试源自人外周血单个核细胞并通过无饲养细胞扩增系统(eNKs)扩增的NK细胞的抗癌效果。结果表明,eNKs对不同卵巢癌异种移植小鼠(即实体瘤、腹部转移瘤和腹水)的肿瘤生长表现出强大的抑制活性,重要的是,呈剂量依赖性。此外,过继转移eNKs可显著减少OC腹膜肿瘤模型中腹水的形成,尤其是减少腹腔内腹水。我们发现,eNKs能够迁移至肿瘤部位,保持其活性,并在皮肤异种移植小鼠中增殖以维持高细胞计数。此外,当以12×10个细胞/小鼠的高剂量增加输注量时,eNK可诱导移植物抗宿主病。这些数据表明,eNK细胞免疫疗法可能是治疗卵巢癌(包括实体瘤和腹水)的一种有前景的治疗策略。