Six-Transmembrane Epithelial Antigen of the Prostate as an Immunotherapeutic Target for Renal Cell and Bladder Cancer

Abstract

T-cell based immunotherapy for renal cell and bladder cancer is one of the most promising therapeutic approaches. STEAP is a novel cell surface protein that is over expressed in various cancers, including renal cell and bladder cancer. Recently we induced STEAP specific helper T lymphocytes that recognize the naturally processed STEAP peptide epitopes STEAP(102-116) and STEAP(192-206) arising from STEAP expressing tumor cells. Thus, STEAP may be a useful tumor associated antigen for designing T-cell based immunotherapy. We determined whether STEAP could induce anti-cellular immune responses to urological cancer. We selected 2 previously described STEAP derived epitope peptides, STEAP(102-116) and STEAP(192-206), and examined their ability to elicit helper T-lymphocyte responses by in vitro vaccination of CD4 T lymphocytes from healthy individuals and patients with cancer. STEAP peptides induced helper T-lymphocyte responses using lymphocytes from healthy individuals that directly recognized STEAP expressing, DR positive renal cell and bladder cancer cells, and autologous dendritic cells pulsed with STEAP expressing tumor cell lysates in a major histocompatibility complex class II restricted manner. These peptides also stimulated T-cell responses in patients with renal cell or bladder cancer. Each STEAP peptides behaved as a promiscuous T-cell epitope, in that they stimulated T cells in the context of multiple major histocompatibility complex class II alleles. Results show that STEAP helper T-lymphocyte epitopes could be used to optimize T-cell based immunotherapy against STEAP expressing renal cell and bladder cancer.