Elsevier

Urology

Volume 51, Issue 1, January 1998, Pages 150-157
Urology

Basic Science
Specific T Cell Recognition of Peptides Derived from Prostate-specific Antigen in Patients with Prostate Cancer

https://doi.org/10.1016/S0090-4295(97)00480-9Get rights and content

Abstract

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 Flu58–66 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 PSA141–150 was observed. The remaining 6 patients had no reactivity with any PSA-derived peptide. The T cell line with specific recognition of peptide PSA141–150 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 Flu58–66.

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.

Section snippets

Patients

All patients had histologically proven prostate adenocarcinoma and were evaluated at the University of Maryland Medical System, Baltimore, Md or Baltimore VA Medical Center for treatment. Patients who agreed to participate were enrolled in an Institutional Review Board-approved protocol for blood and tissue procurement. Patients underwent standard serotyping for HLA A, B, and C alleles. Patients classified as HLA-A2 were offered the opportunity to donate peripheral blood leukocytes by

Peptides

Peptides derived from the sequence of PSA are shown in Table I. These peptides fit the common binding motif for HLA-A2[16]and bound to purified HLA-A2.1 with the affinity shown in Table I using the assay of Ruppert et al.[16]The binding affinity of the synthetic peptides is expressed as the concentration (nM) of peptide required to inhibit 50% of the binding of 125I-FLPSDYFPSV to purified HLA-A2.1 molecules. By the criteria defined by Ruppert et al.,[16]the influenza matrix peptide Flu58–66

Comment

We attempted to determine whether patients with prostate cancer have T cells that can specifically recognize PSA. We examined 7 HLA-A2 patients with prostate cancer by in vitro stimulation of PBMC with peptides derived from PSA and known to bind to HLA-A2. Specific recognition of PSA141–150 was demonstrated in 1 patient who had undergone radical retropubic prostatectomy for clinically localized prostate cancer. We could not demonstrate recognition of endogenous PSA by this T cell line using as

Acknowledgements

Acknowledgment.

To Joyce Kendall, Bernadette O’Connell,and Charles Schiffer for leukopheresis support and to Licia Rivoltini and Mark Mamula for advice and review.

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