Chiang, CLL; Ledermann, JA; Aitkens, E; Benjamin, E; Katz, DR; Chain, BM; (2008) Oxidation of ovarian epithelial cancer cells by hypochlorous acid enhances immunogenicity and stimulates T cells that recognize autologous primary tumor. CLIN CANCER RES , 14 (15) 4898 - 4907. 10.1158/1078-0432.CCR-07-4899.
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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.
|Title:||Oxidation of ovarian epithelial cancer cells by hypochlorous acid enhances immunogenicity and stimulates T cells that recognize autologous primary tumor|
|Keywords:||PULSED DENDRITIC CELLS, PHASE-I TRIAL, ANTI-CD40 MONOCLONAL-ANTIBODY, CARCINOMA PATIENTS, MELANOMA PATIENTS, GENE-THERAPY, PEPTIDE, IMMUNITY, VACCINATION, HER-2/NEU|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of) > Research Department of Immunology|
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > CRUK Cancer Trials Centre
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Pathology
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