Improving Prostate Cancer Outcome with Vectored Vaccines (IMPROVE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Italy,Switzerland
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 8061101.77
EU funding (EUR): 6000000.0
Participants: 7
Project status: CLOSED

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, quantitative analysis of immune effector cells in the prostate following immunotherapy treatment and assess a new predictor of vaccine performance. For the first time, we will evaluate whether checkpoint inhibitor treatment (PD-1 and PD-L1 monoclonal antibodies) can be clinically effective in prostate cancer if it is given in combination with antigen-specific immunotherapy and whether both early and late stage prostate cancer patients can be benefit from it. Tumour burden following immunisation will be measured by serial sampling of the blood for detection and quantification of circulating tumour cells and/or circulating tumour DNA which is a novel accurate and non-invasive method that will provide an early indication of vaccine clinical activity compared to the traditional outcomes of progression free and overall survival in late stage cancer clinical trials. 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.

Keywords: viral vector,cd8 t cell,vaccination,immunogenicity