Tang Choon K, Lodding Jodie, Minigo Gabriela, Pouniotis Dodie S, Plebanski Magdalena, Scholzen Anja, McKenzie Ian F C, Pietersz Geoffrey A, Apostolopoulos Vasso
Immunology and Vaccine Laboratory, Burnet Institute at Austin, Heidelberg, VIC, Australia.
Immunology. 2007 Mar;120(3):325-35. doi: 10.1111/j.1365-2567.2006.02506.x.
Recent years have seen a resurgence in interest in the development of efficient non-viral delivery systems for DNA vaccines and gene therapy. We have previously used oxidized and reduced mannan as carriers for protein delivery to antigen-presenting cells by targeting the receptors that bind mannose, resulting in efficient induction of cellular responses. In the present study, oxidized mannan and reduced mannan were used as receptor-mediated gene transfer ligands for cancer immunotherapy. In vivo studies in C57BL/6 mice showed that injection of DNA encoding ovalbumin (OVA) complexed to oxidized or reduced mannan-poly-L-lysine induced CD8 and CD4 T-cell responses as well as antibody responses leading to protection of mice from OVA+ tumours. Both oxidized and reduced mannan delivery was superior to DNA alone or DNA-poly-L-lysine. These studies demonstrate the potential of oxidized and reduced mannan for efficient receptor-mediated gene delivery in vivo, particularly as DNA vaccines for cancer immunotherapy.
近年来，人们对开发用于DNA疫苗和基因治疗的高效非病毒递送系统的兴趣再度兴起。我们之前曾使用氧化甘露聚糖和还原甘露聚糖作为载体，通过靶向结合甘露糖的受体将蛋白质递送至抗原呈递细胞，从而有效诱导细胞反应。在本研究中，氧化甘露聚糖和还原甘露聚糖被用作受体介导的基因转移配体用于癌症免疫治疗。在C57BL/6小鼠体内的研究表明，注射与氧化或还原甘露聚糖-聚-L-赖氨酸复合的编码卵清蛋白（OVA）的DNA可诱导CD8和CD4 T细胞反应以及抗体反应，从而保护小鼠免受OVA+肿瘤的侵害。氧化和还原甘露聚糖递送均优于单独的DNA或DNA-聚-L-赖氨酸。这些研究证明了氧化和还原甘露聚糖在体内进行高效受体介导的基因递送的潜力，特别是作为癌症免疫治疗的DNA疫苗。
