A NOVEL APPROACH FOR TARGETING DNA TO DENDRITIC CELLS IN VIVO FOR VACCINE DEVELOPMENT AND CANCER IMMUNOTHERAPY

使用被称为DNA的遗传物质作为疫苗，是疫苗接种技术的一项相对较新的进展，具有对抗许多传染病和癌症的潜力。使用DNA的优点是，它可以很容易地进行操作，以开发具有所需的预防和或免疫治疗效果的新疫苗。然而，为了达到最佳效果，用作疫苗的DNA需要针对体内的特定细胞类型。有证据表明，存在于血液和其他组织中的一小部分被称为树突状细胞的细胞在引发DNA疫苗的效果方面发挥了重要作用。然而，目前将DNA传递到这些细胞的方法往往缺乏选择性，或者使用病毒来传递DNA。这可能会引起过敏反应，甚至可能导致肿瘤。使用由磷脂制成的膜状囊泡脂质体作为DNA递送载体最近引起了相当大的兴趣，因为它们被认为是安全的，并且具有递送大量DNA的潜力。虽然DNA可以很容易地包装在脂质体中，但靶向脂质体及其内容物并不容易。包裹的DNA)转移到体内的特定细胞（如树突状细胞）。我们最近生产了一种新的螯合剂脂质分子，它可以方便地附着在脂质体表面的特异性靶向分子上，例如工程形式的抗体片段，它可以靶向或引导脂质体连同它们的有效载荷(例如。（DNA），直接转移到树突细胞。该项目将通过检查含有模型抗原DNA的脂质体是否可用于疫苗接种，以抑制小鼠高度转移性肿瘤（黑色素瘤）的生长和转移，来测试使用这种靶向脂质体作为DNA疫苗的潜力。

The use of genetic material, known as DNA, as a vaccine, has been a relatively new advance in vaccination technology with potential for combating many infectious diseases and cancers. The use of DNA has the advantage that it can be easily manipulated to develop new vaccines that have the desired preventative and-or immunotherapeutic effect. For optimal effect, however, the DNA to be used as a vaccine needs to be targeted to specific cell types in the body. Evidence suggests that a minor population of cells known as dendritic cells, which are present in blood and other tissues, play an important role in eliciting the effects of DNA vaccines. However, current methods for delivering DNA to these cells often lack selectivity in delivery, and-or use viruses to deliver the DNA. This can pose the risk of allergic type reactions and-or possibly cause tumours. The use of small membranous vesicles known as liposomes, made of phospholipids, has recently attracted considerable interest as DNA delivery vehicles, since these are considered safe, and have the potential to deliver large quantities of DNA. Although DNA can easily be packaged inside liposomes, it is has not been easy to target the liposomes and their contents (eg. encapsulated DNA) to specific cells (such as dendritic cells) within the body. We have recently produced a novel chelator lipid molecule which can be used to conveniently attach onto the liposome surface specific targeting molecules, such as engineered forms of antibody fragments, that can target or steer the liposomes together with their payload (eg. the DNA), directly to dendritic cells. This project will test the potential for using such targeted liposomes as DNA vaccines by examining whether liposomes containing DNA for a model antigen can be used in vaccinations to inhibit the growth and metastasis of a highly metastatic tumour (melanoma) in mice.