PMID- 18676764
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20201212
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 15
DP  - 2008 Aug 1
TI  - Oxidation of ovarian epithelial cancer cells by hypochlorous acid enhances 
      immunogenicity and stimulates T cells that recognize autologous primary tumor.
PG  - 4898-907
LID - 10.1158/1078-0432.CCR-07-4899 [doi]
AB  - PURPOSE: Hypochlorous acid, a product of neutrophil myeloperoxidase, is a 
      powerful enhancer of antigen processing and presentation. In this study, we 
      examine whether ovarian epithelial cells (SK-OV-3) exposed to hypochlorous acid 
      can stimulate T cells from patients with ovarian epithelial cancer that recognize 
      common tumor antigens as well as autologous tumor. EXPERIMENTAL DESIGN: T cells 
      from human leukocyte antigen (HLA)-A2(+) and HLA-A2(-) patients or healthy 
      controls were stimulated with autologous dendritic cells cocultured with the 
      generic ovarian tumor line SK-OV-3, previously exposed to hypochlorous acid. 
      RESULTS: Hypochlorous acid-treated SK-OV-3 cells drove expansion of CD8(+) T 
      cells from HLA-A2(+) individuals, which recognized the HLA-A2-restricted tumor 
      antigen epitopes of HER-2/neu (E75 and GP2) and MUC1 (M1.1 and M1.2). Up to 4.1% 
      of the T cells were positive for the HER-2/neu KIFGSLAFL epitope using pentamer 
      staining. Dendritic cells loaded with oxidized SK-OV-3 cells and further matured 
      with CD40 agonistic antibody or monophosphoryl lipid A additionally induced 
      CD4(+) class II-restricted responses. Critically, T cells stimulated with mature 
      oxidized SK-OV-3 (but not a control oxidized melanoma cell line) directly 
      recognized autologous tumor cells isolated from patient ascites. CONCLUSIONS: 
      Immunization with mature dendritic cells loaded with a generic oxidized tumor 
      cell line stimulates a polyclonal antitumor response that recognizes autologous 
      tumor. These findings suggest a new immunotherapeutic strategy to extend 
      remission in ovarian cancer.
FAU - Chiang, Cheryl L-L
AU  - Chiang CL
AD  - Division of Infection and Immunity, University College London, London, United 
      Kingdom.
FAU - Ledermann, Jonathan A
AU  - Ledermann JA
FAU - Aitkens, Egla
AU  - Aitkens E
FAU - Benjamin, Elizabeth
AU  - Benjamin E
FAU - Katz, David R
AU  - Katz DR
FAU - Chain, Benjamin M
AU  - Chain BM
LA  - eng
GR  - Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (CD40 Antigens)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Oxidants)
RN  - 712K4CDC10 (Hypochlorous Acid)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Aged
MH  - CD40 Antigens/biosynthesis
MH  - CD8-Positive T-Lymphocytes/*metabolism
MH  - Dendritic Cells/cytology/metabolism
MH  - Female
MH  - HLA-A2 Antigen/metabolism
MH  - Humans
MH  - Hypochlorous Acid/*pharmacology
MH  - Leukocytes, Mononuclear/cytology
MH  - Middle Aged
MH  - Models, Biological
MH  - Neoplasms, Glandular and Epithelial/*metabolism
MH  - Ovarian Neoplasms/*metabolism
MH  - Oxidants/pharmacology
MH  - Oxygen/chemistry/*metabolism
EDAT- 2008/08/05 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/08/05 09:00
PHST- 2008/08/05 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/08/05 09:00 [entrez]
AID - 14/15/4898 [pii]
AID - 10.1158/1078-0432.CCR-07-4899 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Aug 1;14(15):4898-907. doi: 10.1158/1078-0432.CCR-07-4899.