PMID- 22130160
OWN - NLM
STAT- MEDLINE
DCOM- 20120427
LR  - 20220317
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 35
IP  - 1
DP  - 2012 Jan
TI  - A novel dendritic cell-based immunization approach for the induction of durable 
      Th1-polarized anti-HER-2/neu responses in women with early breast cancer.
PG  - 54-65
LID - 10.1097/CJI.0b013e318235f512 [doi]
AB  - Twenty-seven patients with HER-2/neu overexpressing ductal carcinoma in situ of 
      the breast were enrolled in a neoadjuvant immunization trial for safety and 
      immunogenicity of DC1-polarized dendritic cells (DC1) pulsed with 6 HER-2/neu 
      promiscuous major histocompatibility complex class II-binding peptides and 2 
      additional human leukocyte antigen (HLA)-A2.1 class I-binding peptides. DC1 were 
      generated with interferon-gamma and a special clinical-grade bacterial endotoxin 
      (lipopolysaccharide) and administered directly into groin lymph nodes 4 times at 
      weekly intervals before scheduled surgical resection of ductal carcinoma in situ. 
      Patients were monitored for the induction of new or enhanced antipeptide 
      reactivity by interferon-gamma ELISPOT and enzyme-linked immunosorbentassays 
      performed on Th cells obtained from peripheral blood or excised sentinel lymph 
      nodes. Responses by cytotoxic T lymphocyte against HLA-A2.1-binding peptides were 
      measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or 
      nonexpressing tumor cell lines. DC1 showed surface phenotype indistinct from 
      "gold standard" inflammatory cocktail-activated DC, but displayed a number of 
      distinguishing functional characteristics including the secretion of soluble 
      factors and enhanced "killer DC" capacity against tumor cells in vitro. 
      Postimmunization, we observed sensitization of Th cells to at least 1 class II 
      peptide in 22 of 25 (88%; 95% exact confidence interval, 68.8%-97.5%) evaluable 
      patients, whereas 11 of 13 (84.6%; 95% exact confidence interval, 64%-99.8%) 
      HLA-A2.1 patients were successfully sensitized to class I peptides. Perhaps most 
      importantly, anti-HER-2/neu peptide responses were observed up to 52-month 
      postimmunization. These data show that even in the presence of early breast 
      cancer such DC1 are potent inducers of durable type I-polarized immunity, 
      suggesting potential clinical value for development of cancer immunotherapy.
FAU - Koski, Gary K
AU  - Koski GK
AD  - Department of Biological Sciences, Kent State University, Kent, OH, USA.
FAU - Koldovsky, Ursula
AU  - Koldovsky U
FAU - Xu, Shuwen
AU  - Xu S
FAU - Mick, Rosemarie
AU  - Mick R
FAU - Sharma, Anupama
AU  - Sharma A
FAU - Fitzpatrick, Elizabeth
AU  - Fitzpatrick E
FAU - Weinstein, Susan
AU  - Weinstein S
FAU - Nisenbaum, Harvey
AU  - Nisenbaum H
FAU - Levine, Bruce L
AU  - Levine BL
FAU - Fox, Kevin
AU  - Fox K
FAU - Zhang, Paul
AU  - Zhang P
FAU - Czerniecki, Brian J
AU  - Czerniecki BJ
LA  - eng
GR  - R01 CA096997-03/CA/NCI NIH HHS/United States
GR  - R01 CA096997/CA/NCI NIH HHS/United States
GR  - R01 CA096997-02/CA/NCI NIH HHS/United States
GR  - R01 CA096997-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA096997-04A2/CA/NCI NIH HHS/United States
PT  - Clinical Trial
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 (Lipopolysaccharides)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antigens, Neoplasm/immunology
MH  - Breast Neoplasms/immunology/pathology/*therapy
MH  - Cancer Vaccines/*immunology
MH  - Carcinoma, Ductal/immunology/pathology/*therapy
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Interferon-gamma/immunology/metabolism
MH  - Lipopolysaccharides/immunology/metabolism
MH  - Lymphocyte Activation
MH  - Neoplasm Staging
MH  - Receptor, ErbB-2/immunology
MH  - Th1 Cells/immunology
PMC - PMC3241864
MID - NIHMS329490
EDAT- 2011/12/02 06:00
MHDA- 2012/04/28 06:00
PMCR- 2013/01/01
CRDT- 2011/12/02 06:00
PHST- 2011/12/02 06:00 [entrez]
PHST- 2011/12/02 06:00 [pubmed]
PHST- 2012/04/28 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1097/CJI.0b013e318235f512 [doi]
PST - ppublish
SO  - J Immunother. 2012 Jan;35(1):54-65. doi: 10.1097/CJI.0b013e318235f512.