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Dendritic cells for novel immmunotherapies

Final Report Summary - DC-THERA (Dendritic cells for novel immmunotherapies)

Dendritic cells (DC) are specialised cells of the immune system that trigger and regulate many different types of immune response. It is convenient to view the position of these cells within the immune system as being placed at the intersection of its two main arms, which respectively mediate innate and adaptive immune responses.

Innate immunity is a phylogenetically ancient form of immunity whose origins can be traced back to the earliest living organisms. According to one view, innate immunity is preoccupied with the perception of 'danger', whether as a result of infection or cell or tissue damage. Acting through ancient Pattern recognition receptors (PRRs) that are encoded in the DNA of both invertebrates and vertebrates, the innate arm of immunity can recognise 'danger signals' and trigger specialied responses. These are designed to eliminate different classes of infectious agents, such as viruses, bacteria, fungi and certain parasites, and to aid in repair and healing of damaged tissues.

Because DC play such crucial and pivotal roles in inducing and regulating adaptive immune responses, there is considerable interest in their potential as therapeutic agents. There are good reasons to believe, for example, that DC could potentially be developed as vaccines to trigger protective immunity against cancers, and potentially against infectious agents such as HIV. Alternatively, their regulatory activities might be exploited to overcome aberrant or unwanted immune responses, such as those that lead to allergies, autoimmune diseases or transplant rejection. The ultimate realisation of these goals ('dendritic cells as novel immuntherapies') depends on a translational approach from basic research though pre-clinical models to the clinic, and back again.

As highlighted above, DC immunobiology has enormous potential for development of new immunotherapies such as those for cancer and infectious disease. Europe possesses a critical mass of leaders in the field who have pioneered many innovative advances and provided initial proof of principle for these approaches.

Its original scientific and technological (S&T) objectives were to encourage and facilitate the translation of genomic, proteomic and bioinformatic information, with knowledge from molecular cell biology and pre-clinical models, into therapeutic endpoints focussing on new and continuing clinical trials of DC-based therapies for cancer, and to a lesser extent HIV infection and AIDS.

Over its lifetime DC-THERA created an infrastructure to facilitate collaborative working between its partners and associated partners / third parties, and to capitalise upon, and enhance, their collective and complementary expertise and resources. Towards this end, four thematic S&T clusters were originally defined. A fifth focussed on horizontal measures including the development of technological platforms, provision of new education and training opportunities, incorporation of associated partners / third parties, dissemination of information, and network management. Following a mid-term review of the project, new strategic priorities were identified for the remainder of the contract, requiring the creation of an additional, cross-thematic cluster. Specific milestones and deliverables were defined for each of the 20 work packages within these clusters and, by the end of the project, the majority of these were achieved and completed. Just less half of the network's entire budget of EUR 7.6 million over 66 months was allocated to its individual partners, while the remainder was used to support the horizontal activities and the later strategic priorities. This overall budget distribution is appropriate for a Network of Excellence, as opposed to other types of project that are, for example, designed primarily to fund the research and clinical activities themselves.