Parathyroid hormone-related protein as a common target molecule in specific immunotherapy for a wide variety of tumor types

Abstract

Parathyroid hormone-related protein (PTH-rP) has been considered to be responsible for malignancy-associated hypercalcemia and is thought to participate in pathological changes in bone metastases of cancer. In this study, we determined whether or not PTH-rP could be a common target molecule in specific immunotherapy for patients with a wide variety of tumor types. Various types of tumor cell lines were examined for PTH-rP expression at the mRNA and protein levels by RT-PCR, flow cytometry, and immunocytochemistry. We also determined whether or not cancer-reactive cytotoxic T lymphocytes (CTLs) could be induced from the peripheral blood mononuclear cells (PBMCs) of HLA-A24+ patients with gastric, colon, renal, or cervical cancer by in vitro stimulation with two PTH-rP peptides. As a result, PTH-rP mRNA was expressed in the majority of gastric, breast, lung, colon, cervical, and renal cancer cell lines. Expression of the protein was confirmed by both flow cytometry and immunocytochemistry. Furthermore, PTH-rP peptide-specific and cancer-reactive CTLs were successfully generated from the PBMCs of HLA-A24+ patients with different tumor types using in vitro stimulation with either the PTH-rP(102-111) or PTH-rP(110-119) peptide. These findings indicate that PTH-rP could be a common target molecule in specific immunotherapy for patients with a wide variety of tumor types, particularly bone metastases.