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Development of Cellular Immune Responses against PAX5, a Novel Target for Cancer Immunotherapy

¹ Units of Molecular Haematology and Cancer Biology, Institute of Child Health; ² Department of Haematology, University College London; ³ Department of Histopathology, Great Ormond Street Hospital for Children, London, United Kingdom; and ⁴ Bristol Institute for Transfusion Sciences, Bristol, United Kingdom

Requests for reprints: John Anderson or Owen Williams, Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom. Phone: 44-207-905-2265; Fax: 44-207-813-8100; E-mail: j.anderson{at}ich.ucl.ac.uk, owen.williams{at}ich.ucl.ac.uk.

Key Words: PAX5 • T cells • T-cell clones • Cancer immunotherapy

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. [Cancer Res 2008;68(19):8058–65]

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