Vaccine for Malignant Melanoma
The advent of package holidays sent millions of us to enjoy the novelty of blazing sunshine. As a result, incidence rates for malignant melanoma (skin cancer) are now climbing and are set to treble in thirty years time (CRUK 2004). Although there are now many different treatment approaches, unless the disease is caught early, there is currently no curative treatment available.
Trial One
In August 2007 a three year Phase I/II trial funded by the CVI to investigate the efficacy of treating thirty stage IV malignant melanoma patients who had failed chemotherapy, with a dendritic cell vaccine will end. The trial has already finished recruiting and data is being analysed to determine how well the vaccine has worked to stimulate immunity in these patients. Results so far indicate that patients who have low volume disease and who are largely fit and well, apart from their tumour, have responded well to dendritic cell therapy giving longer survival times than those treated by other therapies. Even patients who have progressed through maximum chemotherapy have responded with stable disease. Responses were most marked in metastases of the lung. Patients reported minimal side effects (common side effects including transient and mild flu-like symptoms and tenderness at the site of vaccination) and an improvement in quality of life with an increase in appetite and subsequent weight gain. Data from this trial will be collated and submitted as a manuscript to a peer-reviewed journal.
Vaccine for Childhood Cancers
Although cancer in children is rare, affecting about 1 in 500 children under the age of 15, it remains the most common cause of death from illness in childhood in the UK. Survival rates have improved dramatically but some children have a less than 10% chance of surviving two years. Furthermore, for many of these cancers the use of conventional chemotherapy has failed to make a significant impact on metastatic cancer (where a tumour spreads beyond its original site) or relapsed cancer (where a tumour comes back).
There is evidence from both human and mouse experiments that immunotherapy, and more specifically dendritic cell vaccines, might have an affect on these childhood cancers. Professor Dalgleish has already treated six children on an ‘informed consent’ basis who had all failed standard therapies using their own resected tumour as a vaccine. In one test patient there has been a dramatic clinical response to vaccination which constitutes a dramatic response rate among patients whose prognosis is otherwise poor.
In August 2007, Professor Dalgleish, in collaboration with two major childhood paediatric centres the Royal Marsden Hospital and Great Ormond Street, will embark on a two year phase I clinical trial to treat twenty patients with osteosarcoma followed later by other sarcoma types. The trial was peer reviewed through Cancer Research UK for funding of the Royal Marsden site and the CVI is providing co-funding for the work to be carried out at St George’s University of London. Alongside this, unique to St Georges, Professor Dalgleish will conduct off-trial treatment of other childhood cancers including neuroblastoma which is expected to provide basic information about the responsiveness of this cancer to the vaccine.
This will be the first trial of its kind in paediatric oncology. Patients will be treated with a course of about ten vaccinations of dendritic cells pulsed with autologous tumour lysate initially every two weeks but gradually dropping to every two months. It is hoped that this vaccine will stimulate an immune response against the tumour. To aid this process the patients will also be given a course of a drug called Interleukin-2 (IL-2) which has stimulatory effects on the immune response. The dose of IL-2 that will be used in this trial has minimal toxicity and is suitable for children.
Aldara / IL-2 Trial – Malignant Melanoma
A phase I clinical trial, funded by the CVI has recently finished which determined the efficacy of Aldara cream topically applied to cutaneous (on the surface) and sub-cutaneous (under the skin) melanoma lesions. In some cases the Aldara cream was applied in conjunction with injections of IL-2 into the melanoma lesion. Clinical results for the trial have recently been submitted for publication and showed that Aldara treatment was effective in controlling the growth of about half of cutaneous melanoma lesions. The lessons learned from the Aldara trial will be applied to later studies, possibly in combination with vaccine therapy.
Off Trial Work
In addition to the clinical trials the CVI provides funding to treat a number of patients “off-trial” on an informed consent basis. Such patients are important to the development of treatments and are selected on the basis that they have clinical features which Professor Dalgleish feels makes them amenable to dendritic cell vaccination. Responses in these patients can give vital clues to new areas of treatment and some of these may be written up as case studies in clinical journals.
Future Trials
