FEAST Newsletter # 17, 09/2005, p.3
A/Prof Miles Prince at the Peter MacCallum Cancer Centre (PeterMac) worked with the European group IDM (Immuno Designed Molecules) in three trials. As part of an FP6 project, IDM invited him to participate. Indeed in the assessment process, the EU said that the fact the PeterMac’s team was examing tracking in Australia was one of the major strengths of the project.
A/Prof Miles Prince is now the Principal Investigator from the only non-EU collaborator group in a 6th Framework programme project aiming to demonstrate the immune and clinical efficacy, reproducibility and feasibility of anticancer cell vaccines (from dendritic cells, DC) . The primary pre-clinical objective of the Programme is to identify the optimum DC vaccination strategy focusing on differentiation and maturation, tumour antigen selection, DC loading, dosing/scheduling and site of administration. The project will lead to production of the DC cellular product for a multi-center phase II clinical trial in patients with prostate cancer. The consortium meets twice a year to discuss outcomes with the next meeting in October in Australia.
The specific objective of the Peter Mac group is to examine the tracking and localisation of DC once administered to the patient. DC will be generated, labelled ex vivo with radioactive agents, administered by various routes then, using nuclear medicine imaging technology, tracked in vivo. This technology enables better understanding of the biodistribution, pharmacokinetics and optimal injection route. One component of the project is to undertake a preliminary study in patients with multiple myeloma prior to the prostate cancer trials.
At least two labels are immediately available for ex vivo labelling of DC cells for subsequent in vivo tracking. These are 18F fluoro-deoxyglucose (18F-FDG), a high resolution label with a short half-life (109.7 mins) being detectable by Positron Emission Tomography (PET). 111Indium oxine is a longer half-life only detectable by conventional planar imaging and by single photon emission computerised tomography (SPECT) and thus of lower resolution than PET. 64Cu is a third label being investigated currently. Non-radioactive methods including the loading of ultra small particles of iron oxide (USPIO) into DC visualized by Magnetic Resonance Imaging (MRI) will also allow long term aggregated cell tracking.
Peter Mac is in a unique position to undertake these studies as it has on-site PET, nuclear medicine and MRI facilities, a cell processing facility and experience in using these labels for human cell tracking.
Prior to the Phase II prostate cancer study utilizing the optimised DC vaccine, a 6 patient Phase I study in multiple myeloma has been developed utilizing the current DC approach (a methodology currently used in a large Phase III study in advanced melanoma). Namely, the monocyte-derived Dendritophage cell vaccine will be tested for tracking. Following treatment with the DC vaccine via various routes of injection, patients are assessed through serial imaging (SPECT or PET) to track the destination of the injected cells. Factors including: DC dose, antigen concentration, effect of maturation, injection route and schedule of immunizations will be examined. To date, the first 6 patients have undergone the vaccinations and successful tracking has been demonstrated. A further 3 patients are now being accrued to examine Copper-labelled DC – pre-clincal data indicates that this may be a superior label to 18F-FDG.
The aim of tracking is to use both qualitative and quantitative approaches to determine the strategy which is most effective in delivering DCs. The data is being correlated with immunological data examining T-cell and humoral responses to vaccination. This information will be used in conjunction with the pre-clinical data being generated by the European partners to develop an optimised vaccination strategy using DC vaccines for prostate cancer.
