Jeon Yong Hyun, Choi Yun, Kim Hyun Joo, Kang Joo Hyun, Kim Chul Woo, Jeong Jae Min, Lee Dong Soo, Chung June-Key
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Mol Imaging. 2007 Sep-Oct;6(5):297-303.
Recently, the use of a cancer deoxyribonucleic acid (DNA) vaccine encoding tumor-associated antigens has emerged as an immunotherapeutic strategy. In this study, we monitored tumor growth inhibition by pcDNA3-hMUC1 immunization in mice using optical imaging. To determine the anti-hMUC1-associated immune response generated by pcDNA3.1 or pcDNA3-hMUC1, we determined the concentration of interferon-gamma (IFN-gamma) protein and CD8+IFN-gamma cell numbers among lymphocytes from the draining lymph nodes of mice immunized with pcDNA3.1 or pcDNA3-hMUC1. After subcutaneously injecting CT26/hMUC1-Fluc into mice immunized with pcDNA3-hMUC1, we monitored in vivo tumor growth inhibition using an optical imaging method. The concentration of IFN-gamma protein in pcDNA3-hMUC1 was higher than that of the pcDNA3.1 group (2.7 < or = 0.08 ng/mL and 1.6 +/- 0.07 ng/mL, respectively, p < .001. The number of hMUC1-associated CD8+IFN-gamma cells in pcDNA3-hMUC1-immunized animals was 30-fold higher than in the pcDNA3.1 group. Bioluminescent images showed tumor growth inhibition in pcDNA3-hMUC1 immunized animals up to 25 days after immunization. A good correlation (r2 = .9076: pcDNA3/hMUC1 group; r2 = .7428: pcDNA3.1 group) was observed between bioluminescence signals and tumor weights in two mice in each group. We conclude that optical bioluminescent imaging offers a useful means of monitoring the antitumor effects of cancer DNA immunization in living animals.
最近,使用编码肿瘤相关抗原的癌症脱氧核糖核酸(DNA)疫苗已成为一种免疫治疗策略。在本研究中,我们利用光学成像监测了pcDNA3-hMUC1免疫小鼠的肿瘤生长抑制情况。为了确定由pcDNA3.1或pcDNA3-hMUC1产生的抗hMUC1相关免疫反应,我们测定了用pcDNA3.1或pcDNA3-hMUC1免疫的小鼠引流淋巴结淋巴细胞中γ干扰素(IFN-γ)蛋白浓度和CD8+IFN-γ细胞数量。在将CT26/hMUC1-Fluc皮下注射到用pcDNA3-hMUC1免疫的小鼠后,我们采用光学成像方法监测体内肿瘤生长抑制情况。pcDNA3-hMUC1中IFN-γ蛋白浓度高于pcDNA3.1组(分别为2.7±0.08 ng/mL和1.6±0.07 ng/mL,p<0.001)。pcDNA3-hMUC1免疫动物中hMUC1相关CD8+IFN-γ细胞数量比pcDNA3.1组高30倍。生物发光图像显示,pcDNA3-hMUC1免疫动物在免疫后长达25天内肿瘤生长受到抑制。在每组的两只小鼠中,生物发光信号与肿瘤重量之间观察到良好的相关性(r2 = 0.9076:pcDNA3/hMUC1组;r2 = 0.7428:pcDNA3.1组)。我们得出结论,光学生物发光成像为监测活体动物中癌症DNA免疫的抗肿瘤效果提供了一种有用的手段。