Plymouth Centre of Excellence Research on Vestibular Schwannomas
Vestibular schwannomas are a common type of tumour causing tinnitus, balance problems and deafness in all patients. These tumours appear to be increasing in frequency and the latest estimate is that one in a thousand of us will be diagnosed with them in our lifetime. The only current therapies are surgery and radiosurgery, neither of which is fully effective and both may cause complications such as facial numbness, facial paralysis, balance problems and hearing loss (all largely irreversible). A recent international meeting (CTF-Children Tumour Foundation) of researchers, clinicians, representatives of the biotechnology industry, and patient advocates has stressed the urgent need to find potential drug targets and accelerate clinical trials for these tumours.
Endogenous retroviral proteins are a novel group of potential immunotherapy and drug targets. Endogenous retroviruses are viruses that over many millions of years have integrated themselves into human genome, now making up 8% of the human genome sequence. Our cells normally prevent these viruses from making proteins but this control breaks down in many diseases, especially cancer. The idea is to either treat patients with antibodies made against these proteins or use the proteins to vaccinate and thus boost the individual’s own immune system. In both cases this hopefully will lead to the death of diseased cells. Also, some groups (including ours) have suggested that the viral proteins may themselves contribute to tumour growth and so blocking their action with a drug may reduce tumour growth.
With funding from an Action on Hearing Loss Flexi Grant last year, our preliminary research suggests that higher levels of endogenous retroviral proteins in vestibular schwannomas contribute to schwannoma growth. We have also successfully inhibited schwannoma growth with anti-retroviral (anti-HIV) drug and antibodies targeting endogenous retroviral proteins. Next, we will confirm and clarity these initial findings so that our pharmaceutical partners will invest in the next stage of clinical trials.
Our approach is based on what we call a human in vitro model. Here, we grow in the laboratory tumour cells that have been taken directly from patients. We then experiment on these to measure the amount of viral proteins being produced and see if and how they contribute to tumour growth. We also measure using a well-established technique called immunohistochemistry (IHC) staining the amount of viral protein in tumour and healthy tissues taken directly from patients.
We have tested various drugs against schwannomas in our in vitro model by collaborating with Astra Zeneca, GlaxoSmithKline, Novartis and Bayer. Clinical trials of two such drugs, Sorafenib and Nilotinib, are currently ongoing at the adjacent Derriford hospital. As soon as we can confirm the impact of our new targets on tumour development in our model, and levels of expression in tumour and healthy tissue, we will contact our established collaborators from these companies and move into clinical trials. We are committed to converting positive research findings into new treatments that will stop tumour growth and improve the life of patients suffering from these tumours.