Cancer is the leading killer. As the population ages and lifespans increase the incidence of cancer will rise. Developing succesful therapies that can halt progression or cure cancer is a major goal of governments in the developed world. Nottingham has had over 30 years of immunotherapy experience, taking a number of these into clinical trials and establishing a SME University Startup (Scancell).
We generate novel Monoclonal antibodies (Mabs) to tumour antigens and utilise these for characterisation of the antigen, identify the role of the antigens in cancer progression and develop novel vaccine strategies for pre-clinical and clinical development. Our close proximity to the clinic and pathology services provide excellent opportunities to bring novel therapeutics to the clinic.
We have successfully delivered both vaccines and antibodies into clinical trials for cancer treatment and have recently established the Nottingham University Therapeutic Antibody Centre (NUTAC).
What we are doing about...
New therapeutic strategies for cancer
Succesful targeting of cancer requires identification of novel antigens that are unique or restricted to cancer cells. We have identifed a number of these and developed a range of techniques that enables us to characterise their role in cancer development.
We then evaluate these antigens as potential therapeutic targets. We have developed strategies for evaluating antibody and or vaccine development.
This has succesfully led to the development of two therapeutic strategies that have been taken forward for clinical development.
- Antibodies generated to tumour glycolipids display potent direct killing effects on target cells. It is not clear if these responses are due to antigen location and density or antibody type and specificity. By engineering antigen expression and antibody structure we can characterise the components of these killing functions and provide a rationale for optimised therapeutic antibodies.
- Glycolipid biology: Tumours express a range of glycolipids that are altered when compared to normal tissues. We utilise a range of biochemical techniques to purify, enrich and label these for optimal formulation for antibody production. These techniques also allow us to purify the antigens and utilise mass spectrometry to characterise the antigens.
- The generation of antibody responses to helper independent antigens (HI) is poorly understood. We can use labelled tumour glycolipids to optimise antigen formulation and immunisation strategies. Utilising confocal microscopy and cell tracking techniques we can characterise the role of different immune cells in HI antibody responses.
- Regulatory T cells can significantly inhibit immune responses to tumours. However little is known regarding the mechanisms controlling their induction? Using antibodies to surface antigens (CD55, CD46, CD28, CD3) we have developed an in vitro model of Tr1 regulatory T cell development. We aim to identify the ontogeny of these Tr1 cells using gene array, CHIP and systematic dissection of the signalling controlling these cells.
1. Clinical trial
Antibodies generated in Nottingham targeting colorectal cancer have been licenced and are in clinical trial. (Reference: SC104/CEP-37250/KHK2804)
2. Spinout company - Scancell Ltd.
The University startup, Scancell Ltd., run by Professor Lindy Durrant, has developed a DNA vaccine strategy which is in Phase I trials in Melanoma (Trial reference: SCIB1 http://clinicaltrials.gov)
Our research has been published in leading peer-reviewed journals such as PLoS One and Clinical and Experimental Immunology.
See more publication details under members' profiles.