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CD 4和CD 8 T细胞的募集;与用于促进DNA/RNA转染的递送技术和将编码的RNA/DNA抗原递送至抗原呈递细胞（APC）相结合，对于有效的疫苗是至关重要的。没有递送系统的简单注射不能捕获足够的APC以产生免疫应答。该项目将联合收割机在药物输送和癌症免疫学方面的世界领先的专业知识相结合。具体而言，我们将测试我们的假设，即通过使用微针和纳米复合物的皮内递送将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复合，我们将优化DNA或RNA聚合物和脂质的比例，以产生一系列纳米复合物。接下来，将在树突细胞中评估纳米复合物的体外摄取和翻译。然后将使用生物发光成像监测RNA和DNA靶向/翻译到体内淋巴组织，并与Scancell合作进行抗肿瘤研究（https：//www.scancell.co.uk/）。该项目是药学院（在2018年QS世界药学和药理学排名中排名第6位）和Scancell（癌症免疫治疗SME）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).