Vaccine Group Current Research
Project One: Improving Vaccines with Compounds that Stimulate NKT Cells
We have shown that we can generate very strong anti-tumour immune responses when our standard dendritic cell vaccine is used in combination with alpha-GalCer (stimulates NKT cells). These results complement our earlier discovery that certain combinations of Toll-like receptor ligands improve dendritic cell activity and will be taken into consideration when formulating our clinical vaccine protocols.
We are collaborating with Prof John Fraser from Auckland University to exploit the potent immune-stimulating activity of superantigens to target tumour antigens to dendritic cells. This is a very effective way of getting the target antigen cross-presented to the T cells that mediate anti-tumour immunity.
It is now clear that the structure of the lipid compounds used to stimulate NKT cells influences the ability of NKT cells to enhance dendritic cell function. We are working with Dr Bridget Stocker and Dr Mattie Timmer, who head the Immunoglycomics research at the Malaghan Institute, to investigate whether novel synthesised glycolipids can be used to optimise NKT cell activity and thus enhance immunity to tumours.
Project Two: Increasing the Potency of Dendritic Cell-based Vaccines for the Treatment of Cancer
One of the main aims of our basic research programme is to increase the potency and efficacy of dendritic cell-based vaccines so that we can stimulate strong, long-lasting anti-tumour immune responses.
In 2008 we made the remarkable discovery that when we injected our dendritic cell-based vaccines, a part of the resulting anti-tumour immune response was stimulated by dendritic cells that were already resident in the host. These resident cells appear to acquire tumour antigens from the injected cells, although the mechanism is unknown. We are currently exploring ways to best exploit the activity of the resident dendritic cells in order to get the maximal anti-tumour immune response from our cancer vaccine.
In other work we have been attempting to define the function of different subpopulations of NKT cells to determine which cells we should be targeting in our cancer vaccine protocols. We have shown that a subpopulation of NKT cells containing the CD4 proteins produces a significant quantity of IL-4 in vivo, a factor which may influence the development of Th2-driven diseases such as asthma. This work is currently being prepared for publication.
Project Three: Using Dendritic Cell-based Vaccines in the Clinic
In 2008 we completed our protocol validation studies into the development of dendritic cell-based vaccines for the treatment of glioblastoma multiforme (brain cancer) and hope to treat our first patient in January 2009. It is anticipated that this phase I clinical trial will involve 12-17 patients from the greater Wellington region that meet a strict set of eligibility criteria.
The goal of this study is to determine if vaccination works better when combined with chemotherapy.
Personalised vaccines such as those being used in the brain cancer trial are very intensive to produce, but they do offer a broad immunity that recognises the unique features of an individual patient's tumour tissue. Realistically, well-defined vaccine targets are needed if we are to take vaccination into much larger clinical trials. We therefore intend to work backwards from any patients that show a positive response to the personalised dendritic cell-based vaccine treatment to identify the most effective antigenic targets on their tumour cells. Defined targets that are common to many patients could then be used to develop simpler vaccines with more wide-spread application.
Collaborators
Assoc Prof Rod Dunbar, SBS, The University of Auckland, New Zealand
Prof Vincenzo Cerundolo, University of Oxford, UK
Prof John Fraser, SMS, The University of Auckland, New Zealand
Dr Sarah Hook, Department of Pharmacy, University of Otago, Dunedin, New Zealand
Mr Martin Hunn, Neurosurgeon, Wellington Hospital, New Zealand
Dr Carol Johnson, Dr Catherine Barrow, Dr David Hamilton, Wellington Blood & Cancer Centre, New Zealand
Dr Gavin Painter, Industrial Research Limited (IRL), Wellington, New Zealand
Dr Chris Schmidt, Queensland Institute of Medical Research, Australia
Funding Sources
Cancer Society of New Zealand
Cancer Society Wellington Division
Foundation for Research Science & Technology
Health Research Council of New Zealand
New Zealand Lottery Health Research
University of Otago
