Neo-antigen peptide vaccines as emerging cancer therapeutics

Aging-related diseases, including cancer, will form the major socio-economic health burdens of Western societies this coming century. Enormous expenditure on innovative technologies including combinatorial chemistry, whole genome sequencing, crystallography, high-throughput drug screening and computational science have generated significant advances in understanding the molecular basis of cancer. These advances have rapidly generated hundreds of promising drug leads to key oncogenic targets. However, despite this increased expenditure and research and development (R&D), the number of effective drugs reaching the clinic is in steady decline. There are many possible explanations for this, including political and infrastructure drag. A technical problem is the lack of robust age-dependent, sporadic immune-competent models of human cancer that predict toxicity and response in patients. An ideological hurdle is that, until recently, we have had to use ‘models’ of cancer, such as yeast, worms and flies to identify druggable targets. These models reflect features of a cancer cell but do not mimic tumour tissue in vivo. It is difficult to experimentally model an actual tumour. A tumour could be considered a tissue that includes cancer cells themselves, normal supporting tissue including nutrient conduits, a complex local environment that could be very low in oxygen and many types of immune cells that carry out diverse functions.