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Improving Prostate Cancer Outcome with Vectored Vaccines

Objective

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.

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
Wellington Square University Offices
OX1 2JD Oxford
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 4 663 640,41
Administrative Contact
Stephen Conway (Dr.)

Participants (6)

OXFORD BIOMEDICA (UK) LIMITED
United Kingdom
EU contribution
€ 184 357,59
Address
Oxford Science Park Medawar
OX4 4GA Oxford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Tim Watts (Mr.)
GlaxoSmithKline Vaccines Srl

Participation ended

Italy
EU contribution
€ 72 002
Address
Via Fiorentina
53100 Siena
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Francesco Gulli (Dr.)
UNIVERSITE DE LAUSANNE
Switzerland
EU contribution
€ 600 000
Address
Quartier Unil-centre Bâtiment Unicentre
1015 Lausanne
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Pedro Romero (Dr.)
EXTERNAUTICS SPA

Participation ended

Italy
EU contribution
€ 275 000
Address
Via Fiorentina 1
53100 Siena
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Paolo Sarmientos (Dr.)
DEFINIENS AG
Germany
EU contribution
€ 200 000
Address
Bernhard Wicki Str 5
80636 Munchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Guenter Schmidt (Mr.)
VACCITECH LTD
United Kingdom
EU contribution
€ 5 000
Address
Magdalen Centre 1 Robert Robinson Avenue The Oxford Science Park
OX4 4GA Oxford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Pippa Rathbone (Ms.)