Oxidation of ovarian epithelial cancer cells by hypochlorous acid enhances immunogenicity and stimulates T cells that recognize autologous primary tumor.
OBJECTIVE
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.


METHODS
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.
Chiang
Cheryl L-L
CL
Division of Infection and Immunity, University College London, London, United Kingdom.
Ledermann
Jonathan A
JA
Aitkens
Egla
E
Benjamin
Elizabeth
E
Katz
David R
DR
Chain
Benjamin M
BM
D000368:Aged; D019013:CD40 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008875:Middle Aged; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*
D019013:CD40 Antigens; D015789:HLA-A2 Antigen; D016877:Oxidants; D006997:Hypochlorous Acid; D010100:Oxygen