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Recognition of Prostate and Melanoma Tumor Cells by Six-Transmembrane Epithelial Antigen of Prostate–Specific Helper T Lymphocytes in a Human Leukocyte Antigen Class II–Restricted Manner

Departments of ¹ Pathology, ² Dermatology, and ³ Urology, Asahikawa Medical College, Asahikawa, Japan; and ⁴ Immunology Program and Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida

Requests for reprints: Esteban Celis, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-745-1925; E-mail: ecelis{at}moffitt.org.

The six-transmembrane epithelial antigen of prostate (STEAP) protein is an attractive candidate for T cell–based immunotherapy because it is overexpressed in prostate cancer and various other tumor types. Several peptide epitopes capable of stimulating CTLs that killed STEAP-expressing tumor cells have been described. Our goal was the identification of helper T lymphocyte (HTL) epitopes of STEAP for the optimization of T cell–based immunotherapies against STEAP-expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in silico algorithms for HLA class II–binding peptides and were tested for their ability to elicit HTL responses by in vitro peptide vaccination of CD4 T lymphocytes from healthy individuals and prostate cancer patients. Two peptides (STEAP_102–116 and STEAP_192–206) were effective in stimulating in vitro antitumor HTL responses in both normal individuals and prostate cancer patients. Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because they stimulated T cells in the context of more than one MHC class II allele. These newly described STEAP HTL epitopes could be of value for the design and optimization of T cell–based immunotherapy against STEAP-expressing tumors. [Cancer Res 2007;67(11):5498–504]

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