Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer.
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.
Perambakam
Supriya
S
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.
Xue
Bao-Hua
BH
Sosman
Jeffrey A
JA
Peace
David J
DJ
D000368:Aged; D002857:Chromium / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000097:blood*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000939:Epitopes; D010455:Peptides; D002857:Chromium; D015847:Interleukin-4; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen