title: Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2.
abstract: PAX2 is a transcription factor and member of the highly conserved family of paired box genes. PAX2 is aberrantly expressed in a variety of solid and hematologic malignancies. PAX2 regulates the transcription factor Wilms tumor gene 1, which is a promising target of cancer immunotherapy. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of PAX2 which could be useful for cancer immunotherapy. Thirteen potential HLA-A*0201 epitopes were predicted by a major histocompatibility complex binding algorithm (SYFPEITHI) and a proteasome cleavage algorithm (PAProC) and screened for recognition by T cells from HLA-A*02-positive cancer patients using intracellular cytokine cytometry. Epitope-specific T cells were generated from CD4CD25 regulatory T-cell-depleted peripheral blood mononuclear cell. Nine of 20 colorectal cancer patients, 1 of 13 renal cell carcinoma patients, and 2 of 17 lymphoma patients had a spontaneous CD8 T-cell response toward at least 1 of 6 PAX2 peptide pools. None of the 20 healthy subjects showed reactivity toward PAX2. PAX2.337-345 (TLPGYPPHV)-specific T cells could repeatedly be generated, which specifically lysed the PAX2 expressing colorectal tumor cell line SW480. In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*0201 restricted T-cell epitope and natural ligand of the tumor antigen PAX2. Thus, PAX2 is another embryonic transcription factor, which is of potential interest as immunotherapy target antigen.
authors.affiliation: Hämatologie und Onkologie, Charité Campus Benjamin Franklin, Hindenburgdamm, Germany.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Asemissen
authors.forename: Doreen
authors.initials: D
authors.lastname: Haase
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Antonia
authors.initials: A
authors.lastname: Busse
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen