Immuno-virotherapy for haematological malignancies and metastatic disease

Rationale

A range of cancer-killing viruses have been tested in patient clinical trials, they are safe, well-tolerated and have induced durable clinical response in patients with cancer. Cancer-killing viruses are thought to induce their anti-cancer effects by two distinct mechanisms:

  1. direct killing of cancer cells
  2. activation on the patient’s immune cells to kill the cancer.   

The potential of viruses against some cancer types (i.e. brain and skin cancers) has been heavily reported, however, their usefulness against other cancer types, including blood borne cancers, is less clear. The aim of this project is to expand our knowledge of a range of therapeutic viruses and explore the possibility of using them to treat blood-borne cancers, such as leukaemia, and cancers that have spread to different sites within the body, away from the primary cancer. We hope to identify the mechanisms by which viruses induce their anti-cancer effects and develop novel combination therapies to enhance tumour cell killing. 

In the body, cancer cells do not exist in isolation but in a complex network with other cells including, blood vessels, immune cells and fibroblasts, all of which can support or impede tumour survival and growth. Whilst in vitro human cancer cell line models can mimic certain aspects of the tumour environment they are limited as they do not:

  1. contain a full repertoire of immune cells, which could enhance or inhibit virus therapy
  2. mimic the supportive 3-dimensional cell-to-cell interactions that exist within a developing tumour. 

 Therefore, the use of mice is necessary for this research they allow us to test the efficacy of virus treatment in cancer models which are more representative of human disease. 

Plan of work and impact of our studies

Most of the animals used in this study will be wild type because they have a normal immune system, however, a small number will be immune-deficient as these enable us to examine the mechanisms involved in successful treatments.  Animals will be injected with tumour cells to mimic cancer in the blood or at different sites within the body, such as within the bone. Mice will subsequently be treated with viruses and/or other treatments and tumour growth will be monitored.  

Animal welfare

Throughout these studies all mice will be observed daily to check for signs of distress of adverse effects of tumour growth and/or treatments. All mice will be killed humanely if the health or well-being of the animal is affected and mice will experience no more than moderate adverse effects as a result of this research. Only work that has been tested in human in vitro models, and that has looked promising as the therapeutic approach, will be tested in mouse models.

The overall aim of the project is to identify novel treatments for poor prognosis cancer patients and provide new treatment options for frail/elderly patients which are not eligible for current therapies.

Non-technical summary 

Read immuno-virotherapy for haematological malignancies and metastatic disease non-technical summary (PDF).

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