Zeng Bin, Liao Ai-jun, Lu Fang-gen, Fang Wei-yi, Wang Jian
Department of Gastroenterology, the First Hospital of Nanhua University, Hengyang, China.
Zhonghua Zhong Liu Za Zhi. 2010 Feb;32(2):98-102.
To investigate the antitumor immune response induced by dendritic cells vaccine coding AFPcDNA fragment with signal peptide (AFP(1)) and without signal peptide (AFP(2)), and to determine the inhibiting effect of the vaccine on the growth of hepatocarcinoma xenograft in Balb/c mice.
pcDNA3.1/AFP(1) and pcDNA3.1/AFP(2) were transfected into dendritic cells (DCs) by calcium phosphate nanoparticles and became DCs vaccine. Mouse spleen lymphocytes were stimulated by AFP(1)/DC and AFP(2)/DC. A Balb/c mouse model bearing mouse HCC xenograft was established on the day 14 after transplantation. Forty mice were divided equally into AFP(2)/DC group, AFP(1)/DC group and plasmid control group. The treated mice received DCs vaccine and the same amount of control plasmid.
AFP(2)/DC stimulated T lymphocytel proliferation in vitro and improved CTL activity. The effects were better than AFP(1)/DC. The tumor-bearing mice injected intralesionally with AFP(1)/DC and AFP(2)/DC at a dose of 0.5 ml per mouse showed inhibition of tumor growth and prolongation of survival time. The tumor inhibition rate of the AFP(2)/DC group was 79.2% and the AFP(1)/DC group was 39.7% at 2 weeks after treatment. The tumor volume of AFP(2)/DC group was (726.7 +/- 298.2) mm(3), significantly smaller than the (1486.2 +/- 457.2) mm(3) of the AFP(1)/DC group and (2137.2 +/- 547.2) mm(3) of the plasmid control group (P < 0.05). The mean survival time of mice in the AFP(2)/DC group [(58.5 +/- 4.2) d] and AFP(1)/DC group [(45.2 +/- 4.8) d] were significantly longer than that of plasmid control group [(30.6 +/- 6.2) d, P < 0.05]. Bax-positive cell percentage was increased in the xenografts of AFP(2)/DC-treatment group compare with that of plasmid control group.
AFP(2)/DC and AFP(1)/DC vaccines show evident inhibiting effect on the growth of H22 xenograft in Balb/c mice through inducing efficient and specific immune response against the hepatocarcinoma cells.
研究编码有信号肽的甲胎蛋白cDNA片段（AFP(1)）和无信号肽的甲胎蛋白cDNA片段（AFP(2)）的树突状细胞疫苗诱导的抗肿瘤免疫反应，并确定该疫苗对Balb/c小鼠肝癌异种移植瘤生长的抑制作用。
采用磷酸钙纳米颗粒将pcDNA3.1/AFP(1)和pcDNA3.1/AFP(2)转染至树突状细胞（DCs），制成DCs疫苗。用AFP(1)/DC和AFP(2)/DC刺激小鼠脾淋巴细胞。移植后第14天建立荷小鼠肝癌异种移植瘤的Balb/c小鼠模型。40只小鼠平均分为AFP(2)/DC组、AFP(1)/DC组和质粒对照组。处理的小鼠接受DCs疫苗和等量的对照质粒。
AFP(2)/DC在体外刺激T淋巴细胞增殖并提高CTL活性。效果优于AFP(1)/DC。以每只小鼠0.5 ml的剂量瘤内注射AFP(1)/DC和AFP(2)/DC的荷瘤小鼠显示肿瘤生长受到抑制且生存时间延长。治疗2周后，AFP(2)/DC组的肿瘤抑制率为79.2%，AFP(1)/DC组为39.7%。AFP(2)/DC组的肿瘤体积为(726.7±298.2)mm³，明显小于AFP(1)/DC组的(1486.2±457.2)mm³和质粒对照组的(2137.2±547.2)mm³（P<0.05）。AFP(2)/DC组[(58.5±4.2)d]和AFP(1)/DC组[(45.2±4.8)d]小鼠的平均生存时间明显长于质粒对照组[(30.6±6.2)d，P<0.05]。与质粒对照组相比，AFP(2)/DC治疗组异种移植瘤中Bax阳性细胞百分比增加。
AFP(2)/DC和AFP(1)/DC疫苗通过诱导针对肝癌细胞的高效特异性免疫反应，对Balb/c小鼠H22异种移植瘤的生长显示出明显的抑制作用。
