PMID- 16596621
OWN - NLM
STAT- MEDLINE
DCOM- 20060711
LR  - 20141120
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 106
IP  - 11
DP  - 2006 Jun 1
TI  - Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast 
      cancer vaccine trial.
PG  - 2309-17
AB  - BACKGROUND: E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted 
      immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based 
      vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. 
      The purpose of this study was to further investigate GP2 for potential use in 
      vaccination strategies. Importantly, a naturally occurring polymorphism (I-->V at 
      position 2, 2VGP2) associated with increased breast cancer risk was addressed. 
      METHODS: Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer 
      patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with 
      autologous dendritic cells (DC) pulsed with GP2 and tested in standard 
      cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 
      targets. Additional cytotoxicity experiments used effectors stimulated with DC 
      pulsed with E75, GP2, or the combination of E75+GP2. RESULTS: GP2-stimulated 
      prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and 
      the HLA-A2- control target SKOV3 of 28.8+/-3.7% (P<.01), 29.5+/-4.0% (P<.01), and 
      16.9+/-2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells 
      lysed HER2/neu+ targets at 43.8+/-5.2% versus 44.2+/-5.7% for E75 (P=.87). When 
      combined, an additive effect was noted with 58.6+/-5.4% lysis (P=.05). 
      GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6+/-5.7%) 
      and 2VGP2-loaded T2 targets (17.7+/-5.2%). CONCLUSIONS: GP2 is a clinically 
      relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. 
      Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; 
      therefore, a GP2 vaccine should be effective in patients carrying this 
      polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
AD  - Clinical Breast Care Project, Department of Surgery, Walter Reed Army Medical 
      Center, Washington, DC, USA.
FAU - Storrer, Catherine E
AU  - Storrer CE
FAU - Foley, Rebecca J
AU  - Foley RJ
FAU - Harris, Katie
AU  - Harris K
FAU - Jama, Yusuf
AU  - Jama Y
FAU - Shriver, Craig D
AU  - Shriver CD
FAU - Ponniah, Sathibalan
AU  - Ponniah S
FAU - Peoples, George E
AU  - Peoples GE
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HER-2 peptide E75 (369-377), human)
RN  - 0 (HER2-neu-derived peptide (654-662))
RN  - 0 (Peptide Fragments)
RN  - 0R0008Q3JB (Chromium)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/immunology/*therapy
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*therapeutic use
MH  - Chromium/metabolism
MH  - Dendritic Cells/immunology
MH  - Epitopes/immunology
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/immunology/therapy
MH  - Peptide Fragments/*immunology/therapeutic use
MH  - Receptor, ErbB-2/*immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Tissue Donors
MH  - Tumor Cells, Cultured
EDAT- 2006/04/06 09:00
MHDA- 2006/07/13 09:00
CRDT- 2006/04/06 09:00
PHST- 2006/04/06 09:00 [pubmed]
PHST- 2006/07/13 09:00 [medline]
PHST- 2006/04/06 09:00 [entrez]
AID - 10.1002/cncr.21849 [doi]
PST - ppublish
SO  - Cancer. 2006 Jun 1;106(11):2309-17. doi: 10.1002/cncr.21849.