title: Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro.
abstract: Tumour-derived chaperone-rich cell lysate (CRCL), which is made up of numerous heat shock proteins, has been used successfully to generate tumour-specific T cell responses and protective immunity against a wide range of murine tumours. In this study, we have investigated the potency of human ovarian cancer-derived CRCL to activate dendritic cells (DC) and to generate tumour-specific T cells in vitro. CRCL was generated from primary ovarian cancers and SKOV3-A2, a HER2/neu, Wilm's tumour gene 1 (WT1) and human leucocyte antigen (HLA)-A2 positive human ovarian tumour cell line. Peripheral blood mononuclear cells from both HLA-A2(+) healthy donors and HLA-A2(+) ovarian cancer patients were stimulated weekly with autologous DC loaded with ovarian tumour-derived CRCL. After four to six stimulations in vitro, specific cytokine secretion and cytotoxicity were measured. CRCL promoted interleukin (IL)-12 secretion and enhanced the immunostimulatory capacity of DC. T cells from healthy controls and from ovarian cancer patients secreted higher amounts of interferon-gamma following in vitro restimulation with ovarian cancer-derived CRCL than with HER2/neu or WT1 peptide-pulsed DC. We were also able to generate cytotoxic T lymphocyte activity against cancer-specific antigens such as HER2/neu and WT1 from all healthy donors, but from only one of the four ovarian cancer patients with bulky disease. These preliminary results substantiate further the concept that CRCL may prove to be a potent adjuvant for women suffering from ovarian cancer and that this personalized vaccine may be a promising approach for active immunotherapy.
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, AZ 85724,USA.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Zeng
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Larmonier
authors.forename: M
authors.initials: M
authors.lastname: Sepassi
authors.forename: M W
authors.initials: MW
authors.lastname: Graner
authors.forename: S
authors.initials: S
authors.lastname: Andreansky
authors.forename: M A
authors.initials: MA
authors.lastname: Brewer
authors.forename: E
authors.initials: E
authors.lastname: Katsanis
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D018832:Molecular Chaperones / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015789:HLA-A2 Antigen; D018832:Molecular Chaperones; D018664:Interleukin-12; D007371:Interferon-gamma