Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2.
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.
Asemissen
Anne Marie
AM
Hämatologie und Onkologie, Charité Campus Benjamin Franklin, Hindenburgdamm, Germany.
Haase
Doreen
D
Stevanovic
Stefan
S
Bauer
Sandra
S
Busse
Antonia
A
Thiel
Eckhard
E
Rammensee
Hans-Georg
HG
Keilholz
Ulrich
U
Scheibenbogen
Carmen
C