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OXFORD, United Kingdom

Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 1.79M | Year: 2013

Corneal transplantation is one of the most successful transplant procedures, due mainly to the relatively immune-privileged status of the eye and the fact that the cornea is largely free of blood vessels. However there is a failure rate in the first year of 14% and much higher in high rejection risk patients (such as those with failed previous grafts) due to blood vessel fromation in the patients eye, and the replacment of failed grafts is the indication for corneal transplantation for a significant proportion of patients in several referral centres. The prognosis in these patients can be so poor that many are not offered the opportunity of a further transplant and are left blind. EncorStat® is a novel engineered donor cornea, modified prior to transplantation, to extend rejection-free survival or prevent this risk entirely by suppressing blood vessel formation into the cornea post-transplant. We propose to use TSB funding to complete non-clinical safety studies and gain regulatory approval for clinical evaluation, to produce clinical grade vector and to use this to evaluate EncorStat® in a Phase I/IIa clinical trial.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-2 | Award Amount: 8.06M | Year: 2014

A successful vaccine against cancer is most likely to work through the induction of potent CD8\ T cells that can successfully kill tumour cells. But achieving this has proved difficult and only low level responses are induced by current vaccine approaches. Nonetheless, two therapeutic immunisation strategies have shown partial success in targeting prostate cancer, and one recently reached licensure. Recently, advances in infectious disease vaccinology have identified an exceptionally potent heterologous prime-boost immunisation strategy that has repeatedly induced T cell responses far greater than those observed in cancer immunotherapy. We will test this simian adenovirus MVA approach for the first time in cancer immunotherapy, targeting prostate tumours. We will use an MVA vector encoding the oncofetal antigen 5T4, that has been used safely already in over 500 patients. We will add a priming immunisation with a simian adenovirus aiming to enhance immunogenicity to therapeutic levels. We will use a new accelerated clinical trial design aiming to detect efficacy in relatively early stage prostate cancer patients, exploiting sensitive histological, biochemical and magnetic resonance imaging measures of vaccine efficacy. We will combine this with detailed immunomonitoring, and assess a new predictor of vaccine performance. In parallel, we will undertake detailed pre-clinical comparisons of 5T4 to other leading prostate cancer antigens, including five newly identified prostate-specific antigens, using a well-characterised murine prostate tumour model, exploiting new technologies for maximising CD8\ T cell induction with viral vectors. This SME-led collaboration of two universities with exceptional expertise in vaccinology and immunotherapy, two SMEs with expertise in viral vectored prime-boost immunisation and antigen discovery, and a global pharmaceutical company, will provide complementary abilities to accelerate development of this promising vaccine therapy.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.4-5 | Award Amount: 4.03M | Year: 2008

Curative therapies still do not exist for most CNS diseases but gene therapy is a promising new approach. We propose that it will be possible to modify brain function and pathophysiology by targeted delivery of specific curative factors to selected populations of brain cells that are affected by disease. This opens the door for effective treatment regimes, which can be tailored to individual patients needs. However, currently available gene transfer vectors have limitations regarding safety and efficacy, as they do not allow for targeting of specific populations of neurons or glia or regulation of transgene expression. The NEUGENE consortium has been founded by leading European scientists from academia and industry to overcome these limitations. The consortium will develop Adeno-associated virus (AAV) and Lentivirus (LV)- based tools for targeted and regulated gene transfer into different populations of CNS cells. The consortium will provide a selection of vectors that are optimized for different therapeutic approaches, e.g. regulated expression of neurotrophic factors or manipulation of neurotransmitter synthesis in specific neurons. NEUGENE has three major goals:1) targeting gene transfer vectors to specific populations of neurons and glia, by transcriptional regulation and miRNA-mediated de-targeting and by exploiting the cell-specific tropism of novel types of viral vectors, 2) tight control over expression levels of therapeutic genes by using regulated systems based on different principles, and 3) establishing the safety of the novel vector tools. NEUGENE will verify the functional efficacy of the novel CNS gene transfer tools in a well-established animal model of Parkinsons Disease (PD). This disorder affects over 1.000.000 Europeans and is increasing in prevalence with the aging population. Importantly, principles and mechanisms developed and evaluated within the consortium will also be of direct relevance for gene therapy of many other brain disorder.

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