The aim of our research is to design and develop innovative cancer killing viruses and oncolytic vaccines.
Our research develops anti-cancer viruses that are able to infect and kill cancer cells, while leaving normal cells unharmed. This approach exploits the natural life cycle of the virus, which lyses infected cells in order to release progeny virus particles, allowing the infection to spread from cell to cell through the tumour. The life cycle of some viruses, such as adenoviruses, is intimately dependent on the activities of the cells they infect, and this provides a range of opportunities to engineer viruses that are only active when they encounter the specific environment of a tumour cell.
Adenoviruses can be designed that are dependent on deregulated cell cycle, dysfunctional apoptosis pathways, enhanced glycolytic metabolism and many others. In this way the virus amplifies itself within the tumour, reaching high local concentrations and potentially infecting all tumour cells. In addition this 'oncolytic' type of cell killing is very inflammatory, providing the possibility to create an anti-cancer immune response. These agents are often known as ‘oncolytic vaccines’.
Finally our viruses can be 'armed' to encode additional therapeutic agents, to be expressed only within the tumour; this provides a simple and versatile approach to targeted cancer therapy using a range of potent biological agents.
Leonard Seymour is Professor of Gene Therapies and Director of the Clinical Pharmacology section within the Department of Oncology. He was the Founding President of the British Society for Gene and Cell Therapy, is the Secretary and Trustee of the European Society of Gene and Cell Therapy and an Executive Council Member of the International Society for Cell and Gene Therapy of Cancer. He is Chair of the Scientific Advisory Board of the Chronic Granulomatous Disorder Research Trust, and also chairs the Scientific Advisory Board of the Muscular Dystrophy Consortium. Len is Course Director of the part-time MSc in Experimental Therapeutics, offered by the Department of Oncology in conjunction with the Department for Continuing Education.
Tedcastle A, Illingworth S, Brown A, Seymour L. W. and Fisher, K. D. Actin-resistant DNAse I Expression From Oncolytic Adenovirus Enadenotucirev Enhances Its Intratumoral Spread and Reduces Tumor Growth Molecular Therapy (2016); 24 4, 796–804. doi:10.1038/mt.2015.233. http://dx.doi.org/10.1038/mt.2015.233
Seymour LW, Fisher KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016 Feb 16;114(4):357-61. http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26766734/
Lu W, Chen Q, Ying S, Xia X, Yu Z, Lui Y, Tranter G, Jin B, Song C, Seymour LW, Jiang S. Evolutionarily conserved primary TNF sequences relate to its primitive functions in cell death induction. J Cell Sci. 2016 Jan 1;129(1):108-20. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=26729029
Lynn GM, Laga R, Darrah PA, Ishizuka AS, Balaci AJ, Dulcey AE Pechar M, Pola R, Gerner MY, Yamamoto A, Buechler CR, Quinn KM, Smelkinson MG, Vanek O, Cawood R, Hills T, Vasalatiy O, Kastenmüller K, Francica JR, Stutts L, Tom JK, Ryu KA, Esser-Kahn AP, Etrych T, Fisher KD, Seymour LW, Seder RA. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat Biotechnol. 2015 Nov;33(11):1201-10. http://dx.doi.org/10.1038/nbt.3371