The following trials are due to start during 2007 or 2008.
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.
It is becoming clear that while some patients respond very well to vaccines, others do not. Further research is needed to pin down the best formulation of the vaccine and to identify who will respond and who is responding once treatment has begun. Using the data from trial one in combination with the recent laboratory research data on dendritic cell loading and maturation, a new more effective trial protocol will be developed.
The CVI has agreed to continue its funding for a new three year phase I/II melanoma trial anticipated to start in December 2007 treating a further thirty patients . Decisions about the final combination of treatments awaits the outcome of trial one. However, it is expected that it will involve some of the following approaches: increasing the effectiveness of dendritic cells; removing regulatory cells that damp down immune responses; increasing the effectiveness of the T cells that kill cancers; and combining the vaccine with chemotherapy. It is becoming apparent that vaccines could work much better in combination with other standard treatments and observations support this with marked unexpected responses to chemotherapy, radiotherapy, anti-angiogenic and anti-inflammatory treatments. Use of vaccine in combination with chemotherapy at lower doses may also have fewer toxic side effects for patients.
Prostate Cancer Vaccine
In the UK 1 in 14 men will develop prostate cancer in their lifetime. Indeed, it is the most common form of cancer in men and is the second most common cause of death from cancer for men (Prostate Research Campaign UK). It is currently treated with radiotherapy and hormone therapy and if caught early enough surgery. However, patients that fail hormone therapy have little recourse to other treatment and there is a real need for other forms of intervention.
CVI’s long term financial support has allowed a number of studies to proceed on whole tumour cell vaccination. Out of this original work a small biotech company, Onyvax, was born which has successfully developed a whole cell vaccine to a phase IIb clinical trial for prostate cancer in patients that have failed hormone treatment.
The CVI has agreed to fund a further two year phase I/II trial to investigate ways to improve the efficacy of the Onyvax vaccine. The trial will be conducted on thirty patients with prostate cancer and is due to start in August 2007. Onyvax Ltd will provide the necessary allogeneic tumour cell vaccine which will be combined with agents that should improve the outcome based on preclinical data. The agents include cyclophosphamide (which inhibits T regulatory cells and so aids the stimulation of the immune response) and doxycycline (which inhibits matrix metalloproteases, a class of enzyme involved in various aspects of tumour progression). There is currently no other trial of this kind in prostate cancer.
Mycobacterium Vaccae (M vaccae) in Malignant Melanoma
The CVI recently funded a number of phase I, II and III clinical trials which demonstrated the effectiveness of vaccination with M vaccae in the treatment of melanoma, lung cancer and even breast cancer. M vaccae is similar to the bacterium that causes tuberculosis, but in this formulation (produced to clinical trial standard and heat killed) is completely safe for use in humans. The exact mechanism by which such the treatment works is unclear but it is likely that there is a non-specific recognition of M vaccae which stimulates the relatively suppressed immune system in cancer patients to respond to tumour antigens. Unfortunately, the company supplying the vaccae (SRL172TM) have, until recently, discontinued production. However, an agreement has now been reached with SR Pharma to supply vaccine-quality M vaccae.
The CVI has agreed to fund a two year phase I trial, starting in September 2007, on thirty patients with malignant melanoma using M vaccae and where appropriate in combination with low dose IL-2. This initial trial will be done to batch test the SRL172TM for comparison with previous trials. However, unlike previous trials the aim is to follow immune responses in order to understand the underlying biology in these patients. There are currently no other trials of this kind being undertaken.
Brain Cancer Vaccine
In the UK 16,000 people are diagnosed with a brain tumour each year. It is the second most common cause of cancer mortality in the UK. Aside from primary tumours, 20% of all cancers go on to develop a secondary tumour in the brain. (Brain Research Trust 2007).
Reports in the scientific literature suggest that dendritic cell vaccines have clinical effects in the most common type of brain tumour, malignant glioma, with patients raising immune responses to the vaccines. There is also anecdotal data from Professor Dalgleish’s clinical work to suggest that dendritic cell vaccines give good control of the disease.
In January 2008 Professor Dalgleish, in a multi-centre collaboration with the Royal Marsden University College London and a European colleague, Professor van Gool, aims to undertake a three year Phase I/II clinical trial to treat over 100 brain tumour patients using dendritic cells pulsed with lysate prepared from autologous tumour cells. The CVI will provide the funding for Professor Dalgleish.
