Dou Jun, Hong Xiaowu, Zhao Fengshu, Wang Jing, Chen Junsong, Chen Guobing
Department of Pathogenic Biology and Immunology, Southeast University School of Basic Medical Science, Nanjing, China.
Immunol Invest. 2006;35(2):227-37. doi: 10.1080/08820130600634550.
To assess GM-CSF immune accessory effects in tumor-bearing mice, an animal tumor model was established by inoculating SP2/0 myeloma cells s.c. into the flank of Balb/c mice and 14 days later, injecting either 400 mug recombinant pcDNA3.1/mGM-CSF or a blank plasmid s.c. or i.m. into the tumor four times. The tumor weight, the activities of CTL and NK, the serum levels of IFN-gamma, IL-2 and lymphocytes infiltrating in tumor tissue were analysed 8 weeks later with MTT, ELISA and pathological section methods. The results showed that the tumor lump was reduced in mice injected s.c. (0.880 +/- 0.405 g) or i.m. (0.378 +/- 0.411 g) with pcDNA3.1/mGM-CSF compared with control mice injected s.c. (1.548 +/- 0.221g, P < 0.01)or i.m. (1.554 +/- 0.249g, P < 0.001) with a blank vector. Lymphocyte infiltration in tumor tissues was very apparent in mice injected i.m. with pcDNA3.1/mGM-CSF. In contrast, there was no lymphocyte infiltration in tumor tissues of control mice. In addition, the serum concentrations of IFN-gamma, IL-2 and the activities of CTL and NK cells were significantly increased in mice injected with pcDNA3.1/mGM-CSF compared with a control mice (P < 0.01). In conclusion, direct gene immunization of recombinant pcDNA3.1/mGM-CSF is a feasible strategy for tumor therapy.
为评估粒细胞-巨噬细胞集落刺激因子（GM-CSF）在荷瘤小鼠中的免疫辅助作用，通过将SP2/0骨髓瘤细胞皮下接种至Balb/c小鼠侧腹建立动物肿瘤模型，14天后，将400μg重组pcDNA3.1/mGM-CSF或空白质粒皮下或肌肉注射至肿瘤内，共注射4次。8周后，采用MTT法、ELISA法和病理切片法分析肿瘤重量、细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK）活性、血清干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）水平以及肿瘤组织中浸润的淋巴细胞。结果显示，与皮下注射（1.548±0.221g，P<0.01）或肌肉注射（1.554±0.249g，P<0.001）空白载体的对照小鼠相比，皮下注射（0.880±0.405g）或肌肉注射（0.378±0.411g）pcDNA3.1/mGM-CSF的小鼠肿瘤块减小。肌肉注射pcDNA3.1/mGM-CSF的小鼠肿瘤组织中淋巴细胞浸润非常明显。相比之下，对照小鼠肿瘤组织中无淋巴细胞浸润。此外，与对照小鼠相比，注射pcDNA3.1/mGM-CSF的小鼠血清中IFN-γ、IL-2浓度以及CTL和NK细胞活性显著升高（P<0.01）。总之，重组pcDNA3.1/mGM-CSF直接基因免疫是一种可行的肿瘤治疗策略。
