Nottingham University Research
Cancer Vaccines
A: 105AD7
Professor L Durrant, Dr Ramage, Dr I Spendlove and Professor Rees
The research within the Academic Department of Clinical Oncology and the Institute of Infections Immunity and Inflammation is focused on developing vaccines to stimulate the patients immune response to reject their own cancer. The prototype vaccine 105AD7 targets CD55 and is now in clinical trials in colorectal cancer and osteosarcoma patients. 332 patients have been entered into 4 clinical trials with no associated toxicity, with 80% of patients making an anti-tumour immune response and two children with advanced disease becoming long term survivors. Phase III product registration trials are currently being designed.
The clinical and laboratory experience over the last 5 years has enabled the group to design a novel vaccine concept that overcomes the current limitations of vaccine in the clinic. It has the following design features:
- A Fcy1 region to target dendritic cells in vivo.
- CD4 and CD8 epitopes with mutated anchor residues to give higher binding to MHC and overcome immune ignorance
- Incorporation of functional domains of tumour associated antigens to induce neutralising antibodies
- domain-Fc fusion constructs which can be cloned into viruses, expressed a naked DNA vaccines or produced as fusion proteins to allow effective heterologous prime/boost and maintenance immunisation regimes.
This design has been used to produce a vaccine that stimulates CTL responses in HLA-A2 transgenic mice that recognise and kill endothelial cells over-expressing Tie-2. There is no associated toxicity to normal vasculature. The ability of the vaccine to stimulate anti-tumour immunity in animals is currently being assessed.