Basic ScienceSpecific T Cell Recognition of Peptides Derived from Prostate-specific Antigen in Patients with Prostate Cancer☆
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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R.B.A. is supported by American Cancer Society Institutional Research Grant No. IRG-147, University of Maryland at Baltimore and by a grant from the U.S. Department of Veterans Affairs