CD14 · Innate and adaptive immune responses to nanocell-based tumor-targeted cancer therapeutics

According to the project ‘Fighting against cancer today’ (FACT, funded by the EU 2008), molecularly targeted drugs with associated sophisticated diagnostic systems to personalize care are likely to have a great impact on cancer control in Europe. At the same time, drug delivery is going to be progressed by nanomedicines that can ferry high amounts of active drugs to the tumor. A recent achievement in developing drug delivery systems are bacterially-derived mini- or nanocells that appear to be superior to other nanovector systems, e.g. in terms of stability or packaging versatility, and that aim reaching high therapeutic efficacy with low to no toxicity. This drug-delivery system has been developed by EnGeneIC Pty Ltd in Sydney, Australia. A critical issue of the application of bacterially-derived nanocells to human beings is their inherent capability to provoke adverse immune responses, i.e. via the LPS receptor CD14. Cellular responses to this vector, to be determined as changes in the composition or the activity status of subsets of peripheral blood cells, will be addressed by this proposal. Parallel investigations will yield clues on whether individual genetic variations in molecules determining LPS sensitivity do affect safety and/or efficacy of the delivery system. Moreover, individual genetic variations in drug metabolizing molecules as well as tumor genetics will be assessed in view of therapy outcome predictivity. Research and evaluation of applicability to patients in Europe will be continued at the return host institution, the University Medical Center in Göttingen, which cares for about 13.700 cancer cases yearly, which has a strong focus on molecular tumor diagnostics and individualized medicine within the Department of Gastroenterology, and which provides expertise by experienced specialists as do the German Primate Center or the Max Planck Institutes. Collaborations are strongly envisaged to transfer knowledge most efficiently.