Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24|[plus]| prostate cancer patients

摘要

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24+ prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP36–44 and PTHrP102–111 peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24+ prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8+ T cells. Immunoglobulin G reactive to the PTHrP102–111 or PTHrP110–119 peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP102–111 peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24+ prostate cancer patients with metastases.