B188
Development of cellular immune responses against PAX5; a novel target for cancer immunotherapy
Mengyong Yan, Nourredine Himoudi, Martin Pule
1University College London, London, UK, 2Bristol Institute for Transfusion Sciences, Bristol, UK
PAX5 is a member of the PAX family of developmental transcription factors with an important role in B cell development. Its expression in normal adult tissue is limited to the haemopoietic system but it is aberrantly expressed in a number of solid cancers and leukaemias where it functions as an oncogene. We therefore hypothesized that anti-PAX5 immune responses could be used to target a number of malignancies without significant toxicity. We screened PAX5 peptides for ability to bind HLA-A2, and identified a novel sequence TLPGYPPHV (referred to as TLP). CTL lines against TLP were generated from peripheral blood of 5 normal HLA-A2 positive blood donors and showed specific HLA-A2 restricted killing against PAX5 expressing target cells. We generated high avidity CTL clones from these lines capable of killing cells pulsed with less than 1nM of TLP and killing a range of PAX5 expressing malignant cell lines. Intravenous injection of an anti-PAX5 CTL clone into immunodeficient mice bearing subcutaneous human tumors resulted in specific inhibition of PAX5 expressing tumor growth. This knowledge can be used for the therapeutic generation of CTL lines or the cloning of high avidity T cell receptor genes for use in adoptive immunotherapy.
