PMID- 20103660
OWN - NLM
STAT- MEDLINE
DCOM- 20100422
LR  - 20211020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 3
DP  - 2010 Feb 1
TI  - A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo 
      immunodominant epitope, HER-2/neu88-102.
PG  - 825-34
LID - 10.1158/1078-0432.CCR-09-2781 [doi]
AB  - PURPOSE: Over the past two decades, there has been significant interest in 
      targeting HER-2/neu in immune-based approaches for the treatment of HER-2/neu+ 
      cancers. For example, peptide vaccination using a CD8 T cell-activating HER-2/neu 
      epitope (amino acids 369-377) is an approach that is being considered in advanced 
      phase clinical trials. Studies have suggested that the persistence of 
      HER-2/neu-specific CD8 T cells could be improved by incorporating human leukocyte 
      antigen (HLA) class II epitopes in the vaccine. Our goal in this study was to 
      identify broad coverage HLA-DR epitopes of HER-2/neu, an antigen that is highly 
      expressed in a variety of carcinomas. EXPERIMENTAL DESIGN: A combination of 
      algorithms and HLA-DR-binding assays was used to identify HLA-DR epitopes of 
      HER-2/neu antigen. Evidence of preexistent immunity in cancer patients against 
      the identified epitopes was determined using IFN-gamma enzyme-linked 
      immunosorbent spot (ELIspot) assay. RESULTS: Eighty-four HLA-DR epitopes of 
      HER-2/neu were predicted, 15 of which had high binding affinity for > or =11 
      common HLA-DR molecules. A degenerate pool of four HLA-DR-restricted 15-amino 
      acid epitopes (p59, p88, p422, and p885) was identified, against which >58% of 
      breast and ovarian cancer patients had preexistent T-cell immunity. All four 
      epitopes are naturally processed by antigen-presenting cells. Hardy-Weinberg 
      analysis showed that the pool is useful in approximately 84% of population. 
      Lastly, in this degenerate pool, we identified a novel in vivo immunodominant 
      HLA-DR epitope, HER-2/neu(88-102) (p88). CONCLUSION: The broad coverage and 
      natural immunity to this epitope pool suggests potential usefulness in 
      HER-2/neu-targeting, immune-based therapies such as vaccines.
FAU - Karyampudi, Lavakumar
AU  - Karyampudi L
AD  - Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
FAU - Formicola, Courtney
AU  - Formicola C
FAU - Erskine, Courtney L
AU  - Erskine CL
FAU - Maurer, Matthew J
AU  - Maurer MJ
FAU - Ingle, James N
AU  - Ingle JN
FAU - Krco, Christopher J
AU  - Krco CJ
FAU - Wettstein, Peter J
AU  - Wettstein PJ
FAU - Kalli, Kimberly R
AU  - Kalli KR
FAU - Fikes, John D
AU  - Fikes JD
FAU - Beebe, Melanie
AU  - Beebe M
FAU - Hartmann, Lynn C
AU  - Hartmann LC
FAU - Disis, Mary L
AU  - Disis ML
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Ishioka, Glenn
AU  - Ishioka G
FAU - Knutson, Keith L
AU  - Knutson KL
LA  - eng
GR  - K01 CA100764-05/CA/NCI NIH HHS/United States
GR  - R01 CA113861-04/CA/NCI NIH HHS/United States
GR  - K01 CA100764-03/CA/NCI NIH HHS/United States
GR  - R01-CA113861/CA/NCI NIH HHS/United States
GR  - R41 CA107590-01/CA/NCI NIH HHS/United States
GR  - R41 CA107590/CA/NCI NIH HHS/United States
GR  - R41-CA107590/CA/NCI NIH HHS/United States
GR  - P50 CA116201/CA/NCI NIH HHS/United States
GR  - R01 CA113861-01/CA/NCI NIH HHS/United States
GR  - K01 CA100764/CA/NCI NIH HHS/United States
GR  - K01-CA100764/CA/NCI NIH HHS/United States
GR  - K01 CA100764-06/CA/NCI NIH HHS/United States
GR  - R01 CA113861-03/CA/NCI NIH HHS/United States
GR  - K01 CA100764-02/CA/NCI NIH HHS/United States
GR  - R01 CA113861-02/CA/NCI NIH HHS/United States
GR  - R41 CA107590-02/CA/NCI NIH HHS/United States
GR  - K01 CA100764-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA113861/CA/NCI NIH HHS/United States
GR  - R01 CA113861-05/CA/NCI NIH HHS/United States
GR  - K01 CA100764-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100126
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Immunodominant Epitopes)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Algorithms
MH  - Breast Neoplasms/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Female
MH  - HLA-DR Antigens/*immunology
MH  - Humans
MH  - Immunodominant Epitopes/*analysis
MH  - Ovarian Neoplasms/immunology
MH  - Receptor, ErbB-2/*immunology
PMC - PMC2818599
MID - NIHMS163393
EDAT- 2010/01/28 06:00
MHDA- 2010/04/23 06:00
PMCR- 2011/02/01
CRDT- 2010/01/28 06:00
PHST- 2010/01/28 06:00 [entrez]
PHST- 2010/01/28 06:00 [pubmed]
PHST- 2010/04/23 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - 1078-0432.CCR-09-2781 [pii]
AID - 10.1158/1078-0432.CCR-09-2781 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Feb 1;16(3):825-34. doi: 10.1158/1078-0432.CCR-09-2781. 
      Epub 2010 Jan 26.