Download Jian-Guo Chai Treatment of patients with advanced cancer has

Jian-Guo Chai
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, antigenspecific 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.
Contact details
[email protected]
020 8383 1707
Further information
http://www1.imperial.ac.uk/departmentofmedicine/divisions/immunologyandinflam
mation/immunology/chai/
Clinical specialities relevant to: Cancer, Immunology and Transplantation