Skip to Content

Publications Search - Abstract View

Title: Development of cellular immune responses against PAX5, a novel target for cancer immunotherapy.
Authors: Yan M,  Himoudi N,  Pule M,  Sebire N,  Poon E,  Blair A,  Williams O,  Anderson J
Journal: Cancer Res
Date: 2008 Oct 1
Branches: OEEB
PubMed ID: 18829564
PMC ID: not available
Abstract: 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 hemopoietic system, but it is aberrantly expressed in a number of solid cancers and leukemias 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 the 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 five 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 <1 nmol/L of TLP and killing a range of PAX5-expressing malignant cell lines. I.v. injection of an anti-PAX5 CTL clone into immunodeficient mice bearing s.c. human tumors resulted in specific growth inhibition of PAX5-expressing tumors. 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.