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ADenoViruses as novel clinical treatments

Final Report Summary - ADVANCE (ADenoViruses as novel clinical treatments)

The ADVance consortium consists of 12 partners, representing research in both academia and the industry application domains. The project partners are from the United Kingdom, the Netherlands, France, Hungary, Spain, Switzerland, Sweden and Finland. The Initial Training Network (ITN) is coordinated by Prof Andrew H Baker of the University of Glasgow, UK. A public website for ADVance was created and hosted by the University of Glasgow and was continually updated reflecting the latest network training events and publications. The URL for the website is:
http://www.gla.ac.uk/researchinstitutes/icams/postgraduateresearchopportunities/mariecurieitnadvance/. The partners and their contact information can be found on the ADVance web pages as well as a host of other important ADVance-related information.

ADVance was designed to integrate 8 leading academic centres and 4 private companies under a single umbrella to create an opportunity to train young scientists in adenovirus (AdV) research. Our research and industrial partners represent internationally leading centres of excellence in key facets of research in the basic biology of AdVs and their application as vectors for clinical protocols in cancer, cardiovascular disease and vaccination. This was a wholly unique training opportunity for our research fellows, and indeed the first of its kind across Europe. Our academic and private sector full partners represent key areas critical to improved understanding of adenovirus biology and development of key underpinning technology for translational AdV research at the highest level and together they created a unique training opportunity of the highest calibre. The European space has great strength in adenovirus biology and application, and ADVance has provided important interactions for networking between these Centres of Excellence.

The training components were further complemented by our associated partner EASCO who integrate a broad interdisciplinary training and dissemination programme into ADVance. This ensured the very best training in scientific and key non-scientific skills for each recruited ESR and ER. We were also supported by Prof Glen Nemerow of the Scripps Institute in California as a visiting researcher for his depth of understanding and experience in AdV research spanning many years as well as his very well received “grant writing” session. The fellows benefitted extensively from the complementarity between the host institutes and ADVance’s in-depth strength in training with future careers in mind as well as from fostering long term research links to host institutes and companies.

The network research training was based on a group of well-defined and highly innovative PhD research projects incorporating state-of-the-art methodologies. ADVance has enabled lasting collaborations between partners. The inter-partner secondment plan for the fellows created a critical mass of focused adenovirus biologists and translational scientists and has enabled our young researchers to start an excellent careers in this field.

Scientific and technological objectives
The individual PhD projects undertaken by each of the recruited ADVance fellows aimed to tackle a set of scientific challenges within the field of adenovirus research. Consequently ADVance set out the following scientific and technological objectives:
• To increase our understanding of human and nonhuman AdV biology, tropism and trafficking.
• To develop and assess key technologies that underpin translation of AdVs.
• To develop and test AdVs as oncolytic agents for cancer virotherapy.
• To improve our knowledge of AdV induced immune responses and their use for vaccination.
• To improve and refine the utility of AdVs in cardiovascular research

Progress towards Objectives
The consortium PIs attended the kick off meeting in Umeå, a mid-term review meeting in Paris (coinciding with a training event hosted by EASCO), a final management meeting in Tenerife and further management meetings that have coincided with substantial training events in Zurich, Leiden, Barcelona and Glasgow, the latter dovetailing with a large conference and public engagement activity and in conjunction with another Marie Curie Actions Network called AD-VEC (an IAPP). From an overarching view, through the development and completion of all training, scientific and management objectives, the ADVance project was extremely successful.

Throughout the ADVance project (most fellows were recruited by month 6), fellows benefited from 6 varied and extensive training courses; in Zurich (M12), Leiden (M18), Paris (M24), Kuopio (M25), Barcelona (M32) and Glasgow (M39). The events exposed the fellows to expert insight and training in adenovirus science, its applications relevant to ADVance, industry vs academia discussions for future careers and much more. The Management Board are very grateful for the time and energy that the organisers spent in developing these excellent training events. All ESRs registered on PhD courses either successfully defended their PhD or on track to do so. Upon completion of their ADVance fellowships, Advance ESRs and ERs made varied and challenging career moves. In addition, ADVance ESR Karsten Eichholz won the Prix de Thèse GREMI (Groupe de Recherche et d’Etude des Médiateurs de l’Inflammation), a coveted prize achieved for his thesis work. Taken together, our training programme delivered a broad range of experiences for the fellows and received very positive feedback.

Scientifically, the ITN enabled advancement of adenovirus science across our Centres. We developed a deeper understanding of adenovirus diversity, structure and function. Of particular importance was improving our understanding of basic cell entry mechanisms and interactions with the host – a key area of research into the utility of adenoviruses as gene therapy vectors. One of the great strengths of ADVance has been the interactions with industry – both small and large. We made technological advances in the development of novel adenovirus vectors for a range of applications through this route, including anti-cancer oncolytic advances as well as adenovirus vectors for vaccination and utility for cardiovascular gene therapy. As the ADVance consortium concludes, primary research outcomes will continue. Notably, we have used our collective strength to write a series of state-of-the-art reviews, an attractive outcome for both fellows and PIs. Taken together, ADVance generated scientific impact through continuing primary research papers from contributing groups and commissioned cutting edge review articles.

Final Results and Impact
• Organisation and implementation of 6 training events across sectors
• Effective public engagement by fellows both in their home country and abroad
• Implementation of effective scientific projects for all fellows
• Focused scientific aims and objectives of projects through work package leaders with effective individual project management for each scientific project
• An effective and functional website and varied dissemination activity
• Effective mentoring of fellows and implementation of scientific projects and career plans
• Primary scientific publications, as well as review article scientific publications released as a result of ADVance project

The socio-economic impact of the above is high, since adenoviruses afford novel approaches in the clinical areas of substantial unmet need – in particular, disease areas that we target (cancer, infectious disease and cardiovascular diseases) are globally important diseases that impact upon civilisation worldwide. Consortium members are very active in the implementation of clinical trials with novel adenoviruses developed for such applications. Their development has been central to ADVance and fellows have impacted on this.

Finally, ADVance has fostered long term collaborative opportunities for adenovirus research and development in the future. As the first consortium of its kind, it has catalysed subsequent applications for funding (e.g. ITNs) as well as grants for further development as a direct result of new interactions generated in ADVance. Notably, a sequel to ADVance has been submitted as an ETN (ADVancing; submitted January 2016).