Lei Lei, Li Jianhui, Liu Meiqing, Hu Xiaoming, Zhou Ya, Yang Shiming
Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
School of Optoelectronics, Beijing Institute of Technology, Beijing, China.
Cent Eur J Immunol. 2018;43(2):117-122. doi: 10.5114/ceji.2018.77379. Epub 2018 Jun 30.
CD40L, a costimulatory molecule for dendritic cells (DCs) and B cells, can serve as an adjuvant for enhancing the specific immune response induced by DNA vaccine carrying tumor-associated antigens. In this study, we investigated the potential of CD40L as an adjuvant to enhance the anti-tumor effect mediated by a DNA vaccine based on the Epstein-Barr virus-latent membrane protein 2 (EBV-LMP2) antigen. The plasmids capable of expressing the fusion protein EBV-LMP2-CD40L were constructed. Expression vector pVAX1 and plasmid expressing the individual antigen EBV-LMP2 were used as control groups. These plasmids were used to immunize female BALB/c mice (4-6 weeks old) at days 0, 7 and 14. The results suggest that immunization with DNA vaccines carrying fusion gene EBV-LMP2-CD40L can induce specific immunity more effectively than the plasmid expression individual antigen EBV-LMP2. In order to evaluate the anti-tumor effect of this DNA vaccine, we constructed a tumor bearing mouse model. After immunization, the tumor bearing mouse model, DNA vaccination with EBV-LMP2-CD40L plasmid significantly inhibited tumor growth in the tumor bearing mouse model and enhanced the tumor inhibition rate. This study demonstrated that encoding the EBV-LMP2 tumor antigen within an EBV-LMP2-CD40L DNA vaccine generates an effective antitumor response against EBV tumor, which may be a promising method to improve the antitumor immunity of DNA vaccine.
CD40L是一种用于树突状细胞(DCs)和B细胞的共刺激分子,可作为佐剂增强携带肿瘤相关抗原的DNA疫苗诱导的特异性免疫反应。在本研究中,我们基于爱泼斯坦-巴尔病毒潜伏膜蛋白2(EBV-LMP2)抗原,研究了CD40L作为佐剂增强DNA疫苗介导的抗肿瘤作用的潜力。构建了能够表达融合蛋白EBV-LMP2-CD40L的质粒。将表达载体pVAX1和表达单个抗原EBV-LMP2的质粒用作对照组。在第0、7和14天,用这些质粒免疫雌性BALB/c小鼠(4-6周龄)。结果表明,用携带融合基因EBV-LMP2-CD40L的DNA疫苗免疫比质粒表达单个抗原EBV-LMP2能更有效地诱导特异性免疫。为了评估这种DNA疫苗的抗肿瘤作用,我们构建了荷瘤小鼠模型。免疫后,在荷瘤小鼠模型中,用EBV-LMP2-CD40L质粒进行DNA疫苗接种可显著抑制肿瘤生长并提高肿瘤抑制率。本研究表明,在EBV-LMP2-CD40L DNA疫苗中编码EBV-LMP2肿瘤抗原可产生针对EBV肿瘤的有效抗肿瘤反应,这可能是提高DNA疫苗抗肿瘤免疫力的一种有前景的方法。