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Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer.
Cancer Immunol Immunother. 2002 Jul; 51(5):263-70.CI

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-gamma) 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.

Authors+Show Affiliations

Section of Hematology/Oncology (M/C 734), Room 3150, Molecular Biology Research Building, 900 S. Ashland Avenue, The University of Illinois at Chicago, Chicago, IL 60607, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12070713

Citation

Perambakam, Supriya, et al. "Induction of Tc2 Cells With Specificity for Prostate-specific Antigen From Patients With Hormone-refractory Prostate Cancer." Cancer Immunology, Immunotherapy : CII, vol. 51, no. 5, 2002, pp. 263-70.
Perambakam S, Xue BH, Sosman JA, et al. Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. Cancer Immunol Immunother. 2002;51(5):263-70.
Perambakam, S., Xue, B. H., Sosman, J. A., & Peace, D. J. (2002). Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. Cancer Immunology, Immunotherapy : CII, 51(5), 263-70.
Perambakam S, et al. Induction of Tc2 Cells With Specificity for Prostate-specific Antigen From Patients With Hormone-refractory Prostate Cancer. Cancer Immunol Immunother. 2002;51(5):263-70. PubMed PMID: 12070713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. AU - Perambakam,Supriya, AU - Xue,Bao-Hua, AU - Sosman,Jeffrey A, AU - Peace,David J, Y1 - 2002/04/24/ PY - 2001/10/26/received PY - 2002/02/06/accepted PY - 2002/6/19/pubmed PY - 2002/8/9/medline PY - 2002/6/19/entrez SP - 263 EP - 70 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 51 IS - 5 N2 - 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-gamma) 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. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/12070713/Induction_of_Tc2_cells_with_specificity_for_prostate_specific_antigen_from_patients_with_hormone_refractory_prostate_cancer_ L2 - https://dx.doi.org/10.1007/s00262-002-0281-7 DB - PRIME DP - Unbound Medicine ER -