DU Xiaohui, Wang Xiangyu, Ning Ning, Xia Shaoyou, Liu Juchao, Liang Wentao, Sun Huiwei, Xu Yingxin
General Surgery Department, Chinese PLA General Hospital, Beijing; ; General Surgery Department, Chinese PLA General Hospital Hainan Branch, Hainan;
Exp Ther Med. 2012 Aug;4(2):221-225. doi: 10.3892/etm.2012.579. Epub 2012 May 17.
Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic, however, the distribution of immune cells injected into a tumor-bearing body is unclear. In this study, we investigated the tumor-targeting capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with the near-infrared fluorescent dye DiR. As expected, no significant change in the proliferation rate or antitumor activity of CIK cells and CTLs was noted after labeling with DiR. Furthermore, a gastric carcinoma orthotopic model was established using a fibrinogen-thrombin method in nude mice followed by intraperitoneal infusion of the labeled immune cells into nude mice with established gastric carcinoma. Dynamic tracing of the immune cells was performed using a fluorescence-based live imaging system. Concentrated fluorescence signals were observed for a minimum of two weeks at the tumor site in mice infused with either CIK cells or CTLs with a peak signal at 48 h. Notably, CTLs were more persistent at the tumor site and exhibited a more intense antitumor activity than CIK cells following infusion. These results provided visual evidence of the tumor-targeting capacity of immune cells in live animals.
过继性细胞免疫疗法(ACI)已被证明是一种很有前景的癌症治疗方法,然而,注入荷瘤机体的免疫细胞的分布情况尚不清楚。在本研究中,我们使用近红外荧光成像系统,在人胃癌原位小鼠模型中研究了细胞因子诱导的杀伤细胞(CIK)和细胞毒性T淋巴细胞(CTL)的肿瘤靶向能力。用近红外荧光染料DiR制备CIK细胞和肿瘤特异性CTL。正如预期的那样,用DiR标记后,CIK细胞和CTL的增殖率或抗肿瘤活性没有显著变化。此外,采用纤维蛋白原-凝血酶法在裸鼠中建立胃癌原位模型,然后将标记的免疫细胞腹腔内注入已建立胃癌模型的裸鼠体内。使用基于荧光的实时成像系统对免疫细胞进行动态追踪。在注入CIK细胞或CTL的小鼠的肿瘤部位观察到至少两周的集中荧光信号,在48小时时信号达到峰值。值得注意的是,注入后CTL在肿瘤部位更持久,并且比CIK细胞表现出更强的抗肿瘤活性。这些结果为活体动物中免疫细胞的肿瘤靶向能力提供了可视化证据。