Jung In Hye, Kim DO Hee, Yoo DA Kyung, Baek Sun Young, Jeong Seong Hoon, Jung Dawoon E, Park Seung Woo, Chung Yong-Yoon
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Postgraduate School of Nano Science and Technology, Yonsei University, Seoul, Republic of Korea.
In Vivo. 2018 Jul-Aug;32(4):771-781. doi: 10.21873/invivo.11307.
BACKGROUND/AIM: Natural killer (NK) cells are one of the lymphocytes clinically used for various cancer types. Cytotoxicity of NK cells to cholangiocarcinoma (CC), however, has not yet been studied. Nor NK cell therapy against CC has been clinically applied. In this study, relevance of NK cell therapy for anti-tumor efficacy against CC was pre-clinically investigated.
Human HuCCT-1 cells, an intrahepatic CC cell line, were xenografted into nude mice. The HuCCT-1 tumor-bearing nude mice then received multiple infusions of ex vivo-expanded human NK cells (SMT01) and in vivo cytotoxic activity of the NK cells against the CC cells was evaluated.
SMT01 infusion resulted in significant inhibition of the CC tumor growth. Body weight of the mice administrated with chemotherapy was found to be maintained at the lowest level among all treatment groups while all the SMT01 infusion groups well maintained their body weight.
The present in vivo study demonstrates that NK cells contain cytolytic activity against cholangiocarcinoma and show beneficial effect of NK cell therapy in relevance to quality of life. Further investigation of the NK cell-based immunotherapy can be useful to determine cancer therapeutics for the specific tumor.
背景/目的:自然杀伤(NK)细胞是临床上用于多种癌症类型的淋巴细胞之一。然而,NK细胞对胆管癌(CC)的细胞毒性尚未得到研究。NK细胞疗法针对CC的临床应用也尚未开展。在本研究中,对NK细胞疗法在抗CC肿瘤疗效方面的相关性进行了临床前研究。
将人肝内CC细胞系HuCCT-1细胞异种移植到裸鼠体内。然后,对携带HuCCT-1肿瘤的裸鼠多次输注体外扩增的人NK细胞(SMT01),并评估NK细胞对CC细胞的体内细胞毒性活性。
输注SMT01导致CC肿瘤生长受到显著抑制。发现接受化疗的小鼠体重在所有治疗组中维持在最低水平,而所有输注SMT01的组体重保持良好。
目前的体内研究表明,NK细胞对胆管癌具有溶细胞活性,并且NK细胞疗法在生活质量方面显示出有益效果。进一步研究基于NK细胞的免疫疗法可能有助于确定针对特定肿瘤的癌症治疗方法。