Dr Jian-Guo Chai
Cancer Immunotherapy
Treatment of patients with advanced cancer has been difficult because ‘good’ lymphocytes which attack cancer cells have been overtaken by those ‘bad’ ones that protect cancer cells from being killed. Our research is to test different approaches to boost ‘good’ and diminish ‘bad’ lymphocytes in a pre-clinical experimental model.
Vaccination and adoptive T cell transfer are two basic immunological approaches for the treatment of cancer. Although vaccination strategies are highly effective in inducing robust T cell responses in a non-tolerogenic setting, they are only partially effective in tumour-bearing hosts. The relative inefficiency of vaccination approaches has led us to consider the use of genetically modified, antigen-specific CD8 T cells to optimise adoptive T cell immunotherapy. Genetic modification will be performed by expressing selected exogenous genes or silencing particular endogenous genes.
The male specific minor histocompatibility antigen, HY, has been used as surrogate tumour antigen. The MB49 cell line (murine bladder carcinoma) expresses the Dby, Uty and Smcy genes which encode the CD4 and CD8 T cell epitopes of HY. The available TCR-transgenic mouse lines provide the source of HY-specific CD8 and CD4 T cells which will be subjected to genetic modifications. These genetically modified T cells will be adoptively transferred to tumour-bearing mice to evaluate their anti-tumour activities.
In addition, we have extensively utilized this HY system to investigate a) the kinetics of a successful anti-tumor response including the phenotype and functional characteristics of T cells that destroy tumors; b) the mechanisms of in vivo action of therapeutic monoclonal antibodies; c) the fact of tumour-specific regulatory T cells in tumour-bearing hosts, and d) the distinct behaviors of T cells in response to normal and malignant tissues.
Further information
http://www1.imperial.ac.uk/departmentofmedicine/divisions/immunologyandinflammation/immunology/chai/
Contact details
Email: Jianguo.chai@imperial.ac.uk
Tel: +44(0)20 8383 1707
