Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide.
T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4-CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.
Perambakam
Supriya
S
Department of Medicine, Section of Hematology/Oncology, University of Illinois, Room 3150, Molecular Biology Research Building, 900 South Ashland Avenue, Chicago, IL 60607, USA. speramba@uic.edu
Hallmeyer
Sigrun
S
Reddy
Samarth
S
Mahmud
Nadim
N
Bressler
Linda
L
DeChristopher
Phillip
P
Mahmud
Delores
D
Nunez
Rafael
R
Sosman
Jeffrey A
JA
Peace
David J
DJ
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D000939:Epitopes; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D016233:Immunotherapy, Active / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000008:administration & dosage / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014182:Transplantation, Autologous
D019496:Cancer Vaccines; D000939:Epitopes; D010446:Peptide Fragments; D010455:Peptides; C512543:prostate-specific antigen (146-154); D017430:Prostate-Specific Antigen