title: Pre-clinical assessment of autologous DC-based therapy in ovarian cancer patients with progressive disease.
abstract: Dendritic cell-based vaccines offer promise for therapy of ovarian cancer. Previous studies have demonstrated that oxidation of several antigens, including ovarian cancer cells, using hypochlorous acid strongly enhances their immunogenicity and their uptake and presentation by dendritic cells. The response of T cells and dendritic cells to autologous tumour from patients with active disease has not previously been investigated. Monocyte-derived dendritic cells were generated from patients with active disease and activated by co-culture with oxidised tumour cells and the TLR agonist poly I:C. The dendritic cells showed an activated phenotype, but secreted high levels of TGFβ. Co-culture of the antigen-loaded dendritic cells with autologous T cells generated a population of effector T cells that showed a low level of specific lytic activity against autologous tumour, as compared to autologous mesothelium. The addition of neutralising antibody to TGFβ in DC/T cell co-cultures increased the levels of subsequent tumour killing in three samples tested. Co-culture of monocytes from healthy volunteers with the ovarian cell line SKOV-3 prior to differentiation into dendritic cells reduced the ability of dendritic cells to stimulate cytotoxic effector cells. The study suggests that co-culture of dendritic cells with oxidised tumour cells can generate effector cells able to kill autologous tumour, but that the high tumour burden in patients with active disease may compromise dendritic cell and/or T cell function.
authors.affiliation: Division of Infection and Immunity, University College London, Cruciform Building, Gower Street, London, WC16BT, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hardwick
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ledermann
authors.forename: Egla
authors.initials: E
authors.lastname: Aitkens
authors.forename: Benny
authors.initials: B
authors.lastname: Chain
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D011070:Poly I-C