Abstract
Prostate-specific antigen (PSA) is a potentially useful antigen for targeted T-cell immunotherapy of prostate cancer (CaP). Our laboratory has identified a synthetic nonamer peptide (PSA 146-154) homologue of PSA, which binds to the prevalent human leukocyte antigen, HLA-A2, and elicits specific cytotoxic T-lymphocyte (CTL) responses from normal individuals of the HLA-A2 phenotype. In the present study, we report on the induction of CTL from peripheral blood mononuclear cells (PBMC) of patients with hormone-refractory CaP, which exhibit the same specificity. T-cell lines were established from two patients by stimulation of PBMC with PSA 146-154 peptide in vitro. The T-cell lines exhibited specific cytolytic activity against T2 cells pulsed with PSA 146-154 peptide, but not a control HLA-A2 binding peptide (HIV-RT 476-484) via chromium release assay (CRA). The T-cell lines also showed PSA 146-154 peptide-specific IL-4 responses, but no detectable interferon-gamma (IFN-γ) responses via enzyme-linked immuno-spot assays. Magnetic immuno-selection studies of one of the T-cell lines demonstrated that both cytolytic and interleukin-4 (IL-4) responses were mediated by CD8+, but not by CD4+ T cells. This Tc2 line was further characterized for the ability to recognize endogenously processed PSA epitopes. The line specifically secreted IL-4 in response to HLA-A2+ target cells transfected to express PSA and specifically lysed the PSA+ target cells, but not control transfected cells. The results indicate that the PSA 146-154 peptide emulates a naturally processed and presented peptide epitope of PSA that is within the T-cell repertoire of HLA-A2+ patients with CaP.
Original language | English (US) |
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Pages (from-to) | 263-270 |
Number of pages | 8 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 51 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
Funding
Acknowledgements Human recombinant IL-2 was a generous gift from the National Institute of Healt h Cytokine Program (Bethesda, Md.) and clinical grade recombinant Flt-3 ligand was kindly provided by Immunex (Seattle, Wash.). This study was supported by grants from the Cancer Research Institute (New York City, N.Y.), the Department of Defense Prostate Cancer Research Program (grant no. DAMD 17-98-1-8489), and the National Institute of Health (grant no. R21 CA88062).
Keywords
- HLA-A2
- Immunotherapy
- Interleukin-4
- PSA 146-154 peptide
- Prostate-specific antigen
- Tc2
ASJC Scopus subject areas
- Oncology
- Cancer Research
- Immunology and Allergy
- Immunology