A new paradigm for cancer vaccine delivery: Intradermal lymphatic targeting

已经采取了许多方法来开发刺激细胞免疫反应以根除肿瘤的方法，称为癌症疫苗或免疫疗法。肿瘤表达的抗原的选择和随后的CD4和CD8T细胞的募集；结合用于促进DNA/RNA的转染和将编码的RNA/DNA抗原传递到抗原提呈细胞(APC)的递送技术，对于有效的疫苗是至关重要的。没有递送系统的简单注射无法转染足够的APC来产生免疫反应。该项目将结合世界领先的药物输送和癌症免疫学专业知识。具体地说，我们将测试我们的假设，即通过使用微针和纳米复合体的皮内递送将RNA/DNA靶向淋巴组织将增加APC对RNA/DNA的摄取和翻译。基于DNA/RNA与阳离子聚合物或脂质体的络合作用，我们将优化DNA或RNA聚合物与脂类的比例，以创建一系列纳米复合体。接下来，将在树突状细胞中评估纳米复合体的体外摄取和翻译。然后，生物发光成像将用于监测体内针对淋巴组织的核糖核酸和脱氧核糖核酸靶向/翻译以及与斯坎贝尔(https://www.scancell.co.uk/).)合作进行的抗肿瘤研究这个项目是药学院(在2018年QS药房和药理学世界排名中排名第6)和Sancell(癌症免疫治疗SME)的学者之间的合作。

Numerous approaches have been undertaken to develop ways of stimulating the cellular immune response to eradicate tumours, known as cancer vaccines or immunotherapy. Both the selection of the antigen expressed by the tumour and subsequent recruitment of CD4 and CD8 T cells; in combination with the delivery technology used to promote transfection of the DNA/RNA and delivery of the encoded RNA/DNA antigen to antigen presenting cells (APCs) are vital to an effective vaccine. Simple injection without a delivery system fails to transfect sufficient APCs to generate an immune response. This project is to combine world-leading expertise in drug delivery and cancer immunology. Specifically, we will test our hypothesis that targeting RNA/DNA to lymphoid tissue through the use of intradermal delivery with microneedles and nanocomplexes will increase the uptake and translation of RNA/DNA by APCs. Based on complexation of DNA/RNA with a cationic polymer or liposome, we will optimise the DNA or RNA polymer and lipid ratios to create a range of nanocomplexes. Next, uptake and translation in vitro of the nanocomplexes will be evaluated in dendritic cells. Bioluminescence imaging will then be used to monitor RNA and DNA targeting/translation to lymphoid tissue in vivo and anti-tumour studies conducted in collaboration with Scancell (https://www.scancell.co.uk/). This project is a collaboration between academics in the School of Pharmacy (ranked 6th in the 2018 QS World Rankings for pharmacy and pharmacology) and Scancell (Cancer Immunotherapy SME).