Gao Dong, Cai Yongguang, Chen Yanyuan, Li Wang, Wei Chih-Chang, Luo Xiaoling, Wang Yuhuan
Shenzhen Hornetcorn Biotechnology Co., Ltd., Shenzhen, Guangdong 518045, P.R. China.
The Fifth District of Chemotherapy, Department of Medical Oncology, Central Hospital of Guangdong Provincial Agricultural Reclamation, Zhanjiang, Guangdong 524002, P.R. China.
Oncol Lett. 2018 Apr;15(4):5105-5110. doi: 10.3892/ol.2018.7954. Epub 2018 Feb 5.
Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells. The proportion of GD-induced CD3CD56 CIK and CD3CD56 NK cells was ~4% higher respectively compared with the control. Notably, combination therapy with CIK/NK cells stimulated by GD, markedly suppressed the proliferation of the chronic myelogenous leukemia K562 cell line. Following GD treatment, the cytotoxicity improved by ~25 and 21% when the effector/target ratio was 20:1 and 10:1, respectively. The results of the present study suggested a novel protocol for CIK/NK cell proliferation and revealed that GD may serve as a potent innate and adaptive immunomodulator in immunocyte culture.
Toll样受体（TLR）7/8激动剂已与化疗、放疗或免疫疗法联合应用于淋巴瘤治疗，并用作治疗病毒性皮肤病变和皮肤肿瘤的局部用药。在本研究中，确定了一种腺嘌呤类似物9-（4-羧基苯基）-8-羟基-2-（2-甲氧基乙氧基）-腺嘌呤[称为高冬（GD）]，一种新型TLR7激动剂，在激活细胞因子诱导的杀伤细胞/自然杀伤细胞（CIK/NK）中的作用。本研究结果表明，GD能够激活CIK/NK细胞。与对照组相比，GD诱导的CD3CD56 CIK细胞和CD3CD56 NK细胞比例分别高出约4%。值得注意的是，用GD刺激的CIK/NK细胞进行联合治疗，显著抑制了慢性髓性白血病K562细胞系的增殖。GD处理后，当效应细胞/靶细胞比例为20:1和10:1时，细胞毒性分别提高了约25%和21%。本研究结果提出了一种CIK/NK细胞增殖的新方案，并表明GD可能作为免疫细胞培养中一种有效的先天性和适应性免疫调节剂。
