PMID- 18391753
OWN - NLM
STAT- MEDLINE
DCOM- 20080904
LR  - 20201226
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 31
IP  - 4
DP  - 2008 May
TI  - A multipeptide vaccine is safe and elicits T-cell responses in participants with 
      advanced stage ovarian cancer.
PG  - 420-30
LID - 10.1097/CJI.0b013e31816dad10 [doi]
AB  - Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal 
      carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were 
      eligible to enroll in a phase 1 study designed to assess the safety and 
      immunogenicity of a peptide-based vaccine. Participants received 5 class I major 
      histocompatibility complex-restricted synthetic peptides derived from multiple 
      ovarian cancer-associated proteins plus a class II major histocompatibility 
      complex-restricted synthetic helper peptide derived from tetanus toxoid protein. 
      The vaccines were administered with granulocyte macrophage-colony stimulating 
      factor in Montanide ISA-51 adjuvant over a 7-week period. All vaccine-related 
      toxicities were grade 1 to 2, the most common being injection site reaction 
      (grade 2, 100%), fatigue (grade 1, 78%), and headache (grade 1, 67%). Lymphocytes 
      from the peripheral blood and a node draining a secondary vaccine site (sentinel 
      immunized node) were harvested during the course of vaccination and T-cell 
      responses to the peptides were evaluated using an enzyme-linked immunosorbent 
      spot assay. CD8 T-cell responses were detected in 1 participant ex vivo and in 8 
      of 9 participants (89%) after in vitro stimulation. All 4 HLA-A2 and 
      HLA-A3-restricted peptides were immunogenic. This includes 2 peptides, folate 
      binding protein (FBP191-199) and Her-2/neu754-762, which had not previously been 
      evaluated in vaccines in humans. Responding T cells required over 200 nM for 
      half-maximal reactivity. These data support continued investigation of these 
      peptides as immunogens for patients with ovarian cancer but, owing to low 
      potency, also suggest a need for additional immunomodulation in combination with 
      vaccines to increase the magnitude and to improve the quality of the T-cell 
      responses.
FAU - Chianese-Bullock, Kimberly A
AU  - Chianese-Bullock KA
AD  - Department of Surgery, Division of Surgical Oncology, Human Immune Therapy 
      Center, University of Virginia, Charlottesville, VA 22908, USA. kb9d@virginia.edu
FAU - Irvin, William P Jr
AU  - Irvin WP Jr
FAU - Petroni, Gina R
AU  - Petroni GR
FAU - Murphy, Cheryl
AU  - Murphy C
FAU - Smolkin, Mark
AU  - Smolkin M
FAU - Olson, Walter C
AU  - Olson WC
FAU - Coleman, Elizabeth
AU  - Coleman E
FAU - Boerner, Scott A
AU  - Boerner SA
FAU - Nail, Carmel J
AU  - Nail CJ
FAU - Neese, Patrice Y
AU  - Neese PY
FAU - Yuan, Arlene
AU  - Yuan A
FAU - Hogan, Kevin T
AU  - Hogan KT
FAU - Slingluff, Craig L Jr
AU  - Slingluff CL Jr
LA  - eng
GR  - 5 M01 RR00847/RR/NCRR NIH HHS/United States
GR  - P30 CA44579/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
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 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FUBP1 protein, human)
RN  - 0 (HER-2 peptide E75 (369-377), human)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Melanoma-Specific Antigens)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oleic Acids)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (montanide ISA 51)
RN  - 3OWL53L36A (Mannitol)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.6.4.- (DNA Helicases)
SB  - IM
MH  - Antigens, Neoplasm/administration & dosage/immunology
MH  - *Cancer Vaccines/administration & dosage/adverse effects
MH  - DNA Helicases/administration & dosage
MH  - DNA-Binding Proteins/administration & dosage
MH  - Dose-Response Relationship, Immunologic
MH  - Female
MH  - Humans
MH  - Immunodominant Epitopes/administration & dosage/immunology
MH  - Interferon-gamma/immunology/metabolism
MH  - Mannitol/administration & dosage/adverse effects/analogs & derivatives
MH  - Melanoma-Specific Antigens
MH  - Neoplasm Proteins/administration & dosage/immunology
MH  - Neoplasm Staging
MH  - Neoplasms, Glandular and Epithelial/immunology/pathology/*therapy
MH  - Oleic Acids/administration & dosage/adverse effects
MH  - Ovarian Neoplasms/immunology/pathology/*therapy
MH  - Peptide Fragments/administration & dosage/immunology
MH  - Peritoneal Neoplasms/immunology/pathology/*therapy
MH  - RNA-Binding Proteins
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Treatment Outcome
MH  - *Vaccination/adverse effects
MH  - Vaccines, Subunit/administration & dosage/adverse effects
EDAT- 2008/04/09 09:00
MHDA- 2008/09/05 09:00
CRDT- 2008/04/09 09:00
PHST- 2008/04/09 09:00 [pubmed]
PHST- 2008/09/05 09:00 [medline]
PHST- 2008/04/09 09:00 [entrez]
AID - 00002371-200805000-00011 [pii]
AID - 10.1097/CJI.0b013e31816dad10 [doi]
PST - ppublish
SO  - J Immunother. 2008 May;31(4):420-30. doi: 10.1097/CJI.0b013e31816dad10.