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Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor

Authors' Affiliations: ¹ Division of Infection and Immunity, and Departments of ² Oncology and ³ Histopathology, University College London; and ⁴ Department of Oncology, University College London Hospitals, London, United Kingdom

Requests for reprints: Benjamin M. Chain, Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, United Kingdom. Phone: 44-207-6799402; Fax: 44-207-6799301; E-mail: b.chain{at}ucl.ac.uk.

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.