What do you do when you are faced with terminally ill patients that want to trial a promising immunotherapy but are too sick to provide the immune cells necessary for it to work? If you are Wellington-based Neurosurgeon Mr Martin Hunn, you head back to the laboratory and find another way.
Glioblastoma multiforme (GBM) is a highly aggressive brain tumour, with an extremely poor prognosis.
The standard treatments for GBM are surgery, radiotherapy and chemotherapy, but the tumour rapidly becomes resistant to these therapies, making it ultimately fatal in almost all cases. There is an urgent need to develop novel therapies for this disease.
“We hypothesised that by acting through entirely different mechanisms, therapies that activate the immune system might succeed in attacking GBM tumours where standard treatments have failed,” says Mr Hunn.
Immunotherapy has been explored as a potential treatment option for brain cancers for some time. Here in New Zealand, Mr Hunn, along with colleagues at Wellington Hospital and the Malaghan Institute, recently completed a Phase I GBM vaccine trial at Wellington Hospital, the outcomes of which will be available next year.
The vaccines used in these trials are typically created from the patient’s tumour tissue – the target, and dendritic cells - the immune cells that direct the anti-tumour immune response.
“The problem however is that some GBM patients are so unwell it can be difficult to isolate enough dendritic cells from their blood to prepare a vaccine,” says Mr Hunn.
In parallel to his clinical work, Mr Hunn therefore undertook some laboratory-based research in collaboration with Associate Professor Ian Hermans and colleagues from the Malaghan Institute, to see if they could simplify their approach by removing the need for dendritic cells to be present in the vaccine.
Their research, published recently in the peer-reviewed international journal Clinical Cancer Research, shows that a vaccine consisting of only tumour cells and an immune-boosting adjuvant is an effective treatment for brain tumours (gliomas) in a mouse model.
“Our research has shown that we can evoke a tumour-specific, long-lasting immune response that is strong enough to kill glioma tumours by targeting the activation of dendritic cells already present inside the mouse,” says Mr Hunn. “In some instances we saw the complete disappearance of tumour lesions as detected by magnetic resonance imaging.”
One of the reasons Mr Hunn thinks this new immunotherapy approach has such great promise is because of the adjuvant included in the vaccine to boost the anti-tumour immune response – a compound derived from marine sponges called α-galactosylceramide (α-GalCer).
While this new vaccine therapy has been developed in mice, early indications are that GBM cancer patients have the immune system ‘machinery’ required for the therapy to work equally well in humans.
”We believe our research has identified a simple vaccine that could be an effective treatment for a group of patients who currently face an extremely poor prognosis,” says Mr Hunn.
This research was supported by the Cancer Society of New Zealand, the Neurological Foundation of New Zealand, the Wellington Medical Research Foundation and Just Paterson Real Estate. Mr Hunn was supported by a New Zealand Health Research Council Clinical Fellowship, the Royal Australasian College of Surgeons and the Surgical Research Trust.
Hunn MK, Farrand KJ, Broadley KW, Weinkove R, Ferguson P, Miller RJ, Field CS, Petersen T, McConnell MJ, Hermans IF Vaccination with irradiated tumor cells pulsed with an adjuvant that stimulates NKT cells is an effective treatment for glioma. Clin Cancer Res, 2012 Nov 12 [Epub ahead of print] Link to PubMed abstract.
The Malaghan Institute of Medical Research is New Zealand’s leading vaccine and immunology research institute and is based at Victoria University of Wellington’s Kelburn campus. The Institute operates independently and is a charitable trust. Researchers at the Malaghan Institute are focused on developing innovative ways to harness the strength and potency of the immune system, the body’s own natural defence against disease, to treat cancer, asthma and allergy, arthritis, multiple sclerosis and infectious disease.
Media release issued by Dr Debbie Scarlett, Science Communications Adviser, Malaghan Institute of Medical Research. Contact: firstname.lastname@example.org or (04) 499 6914 ext 896.
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