“Product licensing needs to be ethically accountable, balancing the potential benefits of new medical technologies against the consequence of non-treatment”
With strong pharmacological interests, Len Seymour has focussed his research on improving delivery and selectivity of anticancer therapies. His first contribution was to help define features of the tumour microenvironment that influence drug delivery and accumulation, including aberrant pathways of lymphatic drainage and fluid convection that underlie elevated interstitial fluid pressure, vascular permeability and poor drug penetration. He helped develop a range of innovative therapeutic agents to exploit these insights including polymeric prodrugs, designed for capture within the tumour interstitium and bioreversible activation by tumour-associated enzymes.
Professor Seymour was a key player in developing the principles of RNA and DNA delivery, identifying stabilisation strategies using multivalent polymers to circumvent innate defence mechanisms and achieve the first systemic delivery of DNA.
Seymour then moved into the use of cancer-killing viruses, combining chemical and molecular engineering in developing ‘stealth’ agents for systemic delivery and killing cells by a ‘gain of function’ approach. This technology combines selectivity for the tumour phenotype (selective for specific cellular changes), and provides the highest concentration of therapeutic agent within the tumour, not in the blood, to minimise side effects.
Seymour’s interests embrace genetic engineering to achieve greater selectivity and potency of lytic viruses. For example the inclusion of microRNA-binding sites can lead to site-specific virus attenuation, maintaining anticancer potency whilst increasing safety.
Working with Hybrid Systems, selecting viruses by forced evolution on colorectal cancer cells, Professor Seymour has now produced a lytic adenovirus that kills cells quickly by a process resembling necroptosis, rather than relying on cellular apoptosis mechanisms. This virus appears capable of overcoming pathways of drug resistance and is scheduled for clinical trial in 2011. Preliminary studies suggest the virus may also kill colorectal cancer stem cells.