Specific T cell recognition of peptides derived from prostate-specific antigen in patients with prostate cancer

Objectives. To determine if proteins known to be expressed by both benign and malignant prostate epithelium can be recognized by T cells from patients with prostate cancer. We examined 7 HLA-A2 patients with prostate cancer for evidence of T cell reactivity with prostate-specific antigen (PSA). Methods. Four peptides derived from PSA were chemically synthesized and shown to bind to HLA-A2. As a control, we also examined the immunogenic influenza matrix peptide Flu_58-66 that binds to HLA-A2. These peptides were used to stimulate peripheral blood lymphocytes by in vitro stimulation. Results. In 1 patient, specific recognition of peptide PSA_141-150 was observed. The remaining 6 patients had no reactivity with any PSA-derived peptide. The T cell line with specific recognition of peptide PSA_{141- 150} failed to recognize an autologous B cell blast line expressing endogenous PSA following infection with a recombinant PSA vaccinia virus construct. Three of the 7 patients demonstrated specific reactivity with Flu_58-66. Conclusions. We found specific recognition of one PSA-derived peptide in 1 patient of 7 with prostate cancer. The peptide-specific lymphocyte cell line did not recognize endogenous PSA, suggesting that the peptide may not be produced by prostate cancer cells producing PSA. Specific recognition of PSA peptides was not common in our patients with prostate cancer. Whether such activity can be induced by vaccination strategies or can be therapeutic in men with established prostate cancer remains to be demonstrated.