A new paradigm for cancer vaccine delivery: Intradermal lymphatic targeting

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).