Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
Cancer Gene Ther. 2011 May;18(5):370-80. doi: 10.1038/cgt.2011.13. Epub 2011 Mar 4.
Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.
慢病毒载体是一种有潜力的疫苗传递载体，因为它们可以有效地转导多种非分裂细胞，包括抗原呈递细胞，并且不会引起额外的病毒蛋白表达。为了在保持效率的同时提高安全性，我们通过用源自辛德毕斯病毒的工程化病毒糖蛋白对载体进行假型化，构建了一种树突状细胞（DC）特异性慢病毒载体。我们在小鼠模型中评估了这种编码黑色素瘤抗原 gp100 的工程化慢病毒载体赋予的抗肿瘤免疫水平。与皮下和腹腔注射相比，足垫注射该工程化慢病毒载体可导致最佳的抗原特异性免疫反应。单次接种该工程化慢病毒载体可在接种后 3 周引起高达 10%的外周血 gp100 特异性 CD8+T 细胞，并且这种反应可维持长达 8 周，约为 5%。我们发现这些工程化慢病毒载体引起的抗载体中和抗体反应相对较低。重要的是，直接注射这种工程化慢病毒载体可抑制侵袭性 B16 小鼠黑色素瘤的生长。这些数据表明，DC 特异性慢病毒载体可以成为一种新型的替代疫苗载体，具有为癌症免疫治疗提供有效抗肿瘤免疫的潜力。
