树突状细胞的抗原基因转导及其抗肿瘤免疫作用的研究

Dendritic cells transduced with an adenoviral vector encoding a model antigen induce therapeutic antitumor immunity

目的制备整合素靶向性腺病毒载体RGD-Adv,向树突状细胞(DCs)转导抗原基因,并研究表达特异性抗原DCs的免疫学特点和抗肿瘤效果。方法使用体外连接法构建RGD-Ad,并以流式细胞技术检测其基因转导效率,通过抗原呈递试验、CTL效应试验和小鼠体内抗肿瘤试验考察表达特异性抗原DCs诱导产生CTL效应和在体抗肿瘤作用情况。结果RGD-Adv可安全高效转导DCs,且为病毒载体剂量依赖性;表达特异性抗原DCs能有效诱导抗原特异性CTL效应,并具有显著抗肿瘤效果。结论RGD-Adv是一种理想的载体系统,通过使DCs表达特异性抗原,诱导机体特异性免疫机制,产生抗肿瘤效果,是一种极具前景的肿瘤免疫治疗方法。

Objective To construct integrin-specific adenovirus vectors （RGD-Adv） and compare immunological properties and vaccine efficacy of DCs transduced with foreign gene by Ad-RGD or conventional Ad. Methods RGD-Ad was constructed by in vitro ligation method, and the efficiency of gene transdution was investigated by FACS. The CTL responses and in vivo anti-tumor effects were studied by antigen presentation assay, CTL assay, and in vivo anti-tumor assay. Results RGD-Adv efficiently infected DCs in a vector particle-dependent manner, and induce antigen-specific CTLs response by vaccination. Moreover, vaccination with Ad-RGD infected DCs could achieve greater antitumor effect. Conclusion DCs manipulation using the RGD-Adv could advance the development of more effective vaccines and allow for more convenient adininistration of DCs-based antitumor gene immunotherapy.