PMID- 19483644
OWN - NLM
STAT- MEDLINE
DCOM- 20091005
LR  - 20211020
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 32
IP  - 6
DP  - 2009 Jul-Aug
TI  - Vaccination with agonist peptide PSA: 154-163 (155L) derived from prostate 
      specific antigen induced CD8 T-cell response to the native peptide PSA: 154-163 
      but failed to induce the reactivity against tumor targets expressing PSA: a phase 
      2 study in patients with recurrent prostate cancer.
PG  - 655-66
LID - 10.1097/CJI.0b013e3181a80e0d [doi]
AB  - We conducted a clinical trial of peptide prostate specific antigen (PSA): 154-163 
      (155L) vaccination in human leukocyte antigen (HLA)-A2 patients with detectable 
      and rising serum PSA after radical prostatectomy for prostate cancer 
      (Clinicaltrials.gov identifier NCT00109811). The trial was a single dose-level, 
      phase 2 pilot trial of 1 mg of PSA: 154-163 (155L) emulsified with adjuvant 
      (Montanide ISA-51). The primary endpoint was the determination of immunogenicity 
      of the vaccine; secondary outcomes were determination of toxicity and effect on 
      serum PSA. The vaccine was given subcutaneously 7 times on weeks 0, 2, 4, 6, 10, 
      14, and 18. Peptide-specific CD8 T-cell responses in the peripheral blood 
      mononuclear cells (PBMC) of patients were measured by interferon (IFN)-gamma 
      enzyme-linked immunosorbent spot assay. CD8 T-cell cultures were also established 
      by in vitro stimulation with the peptide presented by autologous dendritic cells. 
      Five patients were enrolled and completed all vaccinations. No IFN-gamma response 
      to PSA: 154-163 (155L) was detected in unfractioned PBMC in any patient either 
      before or after vaccination. Three of 5 patients demonstrated strong IFN-gamma 
      responses to PSA: 154-163 (155L) and native PSA: 154-163 peptides in CD8 T-cell 
      cultures derived from postvaccination PBMC. However, peptide-specific T cells 
      failed to recognize HLA-A2 positive targets expressing endogenous PSA. There were 
      no significant changes in serum PSA level in any subject. No serious adverse 
      events were observed. PSA: 154-163 (155L) is not an effective immunogen when 
      given with Montanide ISA-51. The PSA: 154-163 peptide is poorly processed from 
      endogenous PSA and therefore represents a cryptic epitope of PSA in HLA-A2 
      antigen-presenting cells.
FAU - Kouiavskaia, Diana V
AU  - Kouiavskaia DV
AD  - Division of Urology, Department of Surgery, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA.
FAU - Berard, Carla A
AU  - Berard CA
FAU - Datena, Ellen
AU  - Datena E
FAU - Hussain, Arif
AU  - Hussain A
FAU - Dawson, Nancy
AU  - Dawson N
FAU - Klyushnenkova, Elena N
AU  - Klyushnenkova EN
FAU - Alexander, Richard B
AU  - Alexander RB
LA  - eng
SI  - ClinicalTrials.gov/NCT00109811
GR  - M01 RR016500/RR/NCRR NIH HHS/United States
GR  - M01 RR016500-056966/RR/NCRR NIH HHS/United States
GR  - M01 RR 16500/RR/NCRR NIH HHS/United States
GR  - 6991/PHS HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cancer Vaccines)
RN  - 0 (Peptide Fragments)
RN  - 0 (prostate-specific antigen (154-163))
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Aged
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/adverse effects/*therapeutic use
MH  - Cell Line, Tumor
MH  - Humans
MH  - Interferon-gamma/immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*therapy
MH  - Peptide Fragments/adverse effects/immunology/*therapeutic use
MH  - Pilot Projects
MH  - Prostate-Specific Antigen/adverse effects/immunology/*therapeutic use
MH  - Prostatic Neoplasms/surgery/*therapy
MH  - Vaccination
PMC - PMC2758610
MID - NIHMS117978
EDAT- 2009/06/02 09:00
MHDA- 2009/10/06 06:00
PMCR- 2010/07/01
CRDT- 2009/06/02 09:00
PHST- 2009/06/02 09:00 [entrez]
PHST- 2009/06/02 09:00 [pubmed]
PHST- 2009/10/06 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 10.1097/CJI.0b013e3181a80e0d [doi]
PST - ppublish
SO  - J Immunother. 2009 Jul-Aug;32(6):655-66. doi: 10.1097/CJI.0b013e3181a80e0d.