Community Research and Development Information Service - CORDIS

ERC

ONCOVIRVAX Report Summary

Project ID: 339167
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Mid-Term Report Summary - ONCOVIRVAX (Novel cancer vaccines with virus based cDNA libraries and monitoring for resistant tumour cell populations in prostate cancer)

Prostate cancer is a huge burden of disease in Europe and the world and patients frequently relapse after initial attempts at the cure of localised disease. Cancer vaccination has activity but is only moderately effective. The ERC Advanced Award is using novel translational approaches to take a highly novel vaccine strategy which is excellent in mouse models towards a clinical vaccine for prostate and other cancer patients.

Immunological approaches to cancer have achieved some real success in the last few years. Tumour regression, prolongation of survival and some real increases in cured subpopulations of patients have been achieved in several cancer types, notably melanoma. Factors predicting efficacy remain incompletely understood. Evidence is accumulating that check point inhibitors, as non-antigen specific amplifiers of immune responses, are more likely to work for patients who are mounting an immune response to their tumours – often indicated by an “inflammatory” histological appearance with infiltrating immune response cells, by surrogate biomarkers of such and, to some degree, by the expression of targets for checkpoint inhibition (1 – 10). This new clinical and biological context leads us to modify our strategy so that our vaccine will work as a complementary tool to other immunotherapy by promoting de novo immune responses or enhancing immune responses which may then be amplified for increased clinical impact by non-antigen specific treatments, currently mainly checkpoint inhibitors or cytokines.

Our strategy for our anti-prostate cancer vaccine is based on the expression of cDNA libraries in viral vectors. Using vesicular stomatitis virus (VSV) and prostate and melanoma derived libraries, this is curative in mice and we have established its mechanisms and some key antigenic determinants (11, 12). The ERC Award has so far developed the prostate vaccine strategy in an adenovirus vector and is optimising viral constructs for immunological effect and evaluating these in mouse prostate cancer and human in vitro immune systems. We have the opportunity to evaluate the strategy in glioma in large mammals and we feel this will give us a “translational bridge” to human studies for both safety and efficacy. We have therefore added glioma studies, initially in mice, to the programme of work.

During the initial period of the Advanced Award we have continued to work with three oncolytic virus vectors:

• VSV which provides a well worked up and effective model for the viral cDNA library vaccine and will remain an important tool for studying the mechanisms and the immunobiology of our strategy

• reovirus (Orthoreovirus) which is the clinical grade virus available to us to explore clinical issues and develop our expertise in clinical studies and evaluate routes of administration and tissue penetration. We do not intend to use reovirus to generate viral cDNA library vaccines.

• adenovirus as the preferred eventual vector for our clinical viral cDNA library vaccine programme and most recently we have added Maraba virus (13, 14) to our portfolio as an additional option for clinical viral library vaccine development.

The emergence of resistant populations of tumour cells from heterogeneous human cancers is likely to be a key factor in clinical failure (15). We have studied tumours in mice after treatment with our VSV and adenoviral vaccines using immunological and proteomic approaches to tumours in order to identify potential mechanisms of resistance to the vaccine, and potential blood protein biomarkers of resistance, which will allow us to incorporate strategies to avoid resistance in our clinical programme.

Reported by

UNIVERSITY OF LEEDS ROYAL CHARTER
United Kingdom
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