白细胞介素12
淋巴因子激活杀伤细胞
白细胞介素21
白细胞介素15
癌症研究
NK-92
医学
免疫疗法
人口
免疫学
免疫系统
细胞毒性T细胞
生物
T细胞
白细胞介素
细胞因子
体外
生物化学
环境卫生
作者
Ting Lu,Rui Ma,Anthony G. Mansour,Christian Bustillos,Zhiyao Li,Zhenlong Li,Shoubao Ma,Kun‐Yu Teng,Hanyu Chen,Jianying Zhang,Miguel A. Villalona‐Calero,Michael A. Caligiuri,Jianhua Yu
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2024-05-01
卷期号:: OF1-OF13
标识
DOI:10.1158/2326-6066.cir-23-0324
摘要
Abstract We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18, and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non–small cell lung cancer (NSCLC) in vitro when compared with non-transduced (NT) NK cells, PD-L1+ NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared with NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells in vivo. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).
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