Enhancing the effectiveness of oncolytic virus-induced cancer immunotherapy  Short lay paragraph

The aim of this project is to test the efficacy of oncolytic virus-based anti-cancer therapies and to gain a better understanding of the tumour.

Rationale

We have developed novel therapies for the treatment of cancer. But before clinical translation these need to be validated using mouse models that replicate the complexity of the tumour microenvironment found in humans. Moreover, to design more effective therapies it is essential that we gain a better understanding of the cancer environment.

Plan of work

Mice will be injected with tumour cells and treated with therapeutic agents. The effectiveness of novel treatments will then be examined by monitoring tumour growth (e.g. the amount of tumour) in the presence or absence of treatment. All animals will be killed humanely at the end of each experiment. 

Animal welfare

Tumour growth and the administration of therapeutic agents may cause pain and discomfort, but they are usually well tolerated. Hind-limb paralysis/weakness is a common adverse event in some cancer models, however daily monitoring ensures early detection so mice can be humanely killed.

It is possible, but unlikely, that mice may develop a fever after some treatments or experience weight loss, hunching or tremors. All mice will be monitored daily and humanely killed if they display signs of discomfort.

Three Rs

Replacement

We use a range of human laboratory studies to characterise the cancer microenvironment and the effectiveness of treatments. Animal work will only be carried out when laboratory studies have confirmed that therapeutic strategies are effective against human disease.  

Reduction

Where possible, we will monitor the effect of treatments on tumour growth repeatedly over time in the same animal to avoid unnecessary killing. Moreover, we will ensure that tissue from each animal is fully utilised by sharing excess tissue with other researchers.  Where data on therapeutic efficacy is not available, pilot studies will be carried out to estimate therapeutic benefit and finalise group sizes. 

Refinement

We will use practices that minimise stress, harm and pain. For example, we will use single-use needles to avoid pain from dulled needles and procedures will be performed with anaesthesia or appropriate pain relief if pain is expected. Mice will be monitored daily and humanely killed at the first sign of discomfort.  

Implications

We hope that effective therapeutic strategies will be translated into the clinic to increase patient survival. We also hope to identify safer and more tolerable treatments.