title: A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use.
abstract: In previous studies, we have shown that heat shock protein 70-peptide complexes (HSP70.PCs) derived from the fusion of dendritic cells (DCs) to tumor cells (HSP70.PC-F) possess superior properties compared with HSP70.PCs from tumor cells. HSP70.PC-F are more effective in stimulation of DC maturation and induction of CTL that are able to provide protection of mice against challenge with tumor cells. To develop an improved formulation of HSP70.PC-based tumor vaccine for patient use, we extracted HSP70.PC-F from DCs fused to patient-derived ovarian cancer cells or established human breast cancer cells and examined their properties as tumor vaccines. HSP70.PC-F induced T cells that expressed higher levels of IFN-gamma and exhibited increased levels of killing of tumor cells, compared with those induced by HSP70.PC derived from tumor cells. Enhanced immunogenicity of HSP70.PC-F was associated with improved composition of the vaccine, including increased content of tumor Ags and their processed intermediates, and the detection of other heat shock proteins (HSPs) such as HSP90 and HSP110. The present study has therefore provided an alternative approach to preparation of HSP-based vaccines using DC/tumor fusion technology and gentle and rapid isolation of HSP peptide complexes.
authors: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. jgong@bu.edu
authors: Jianlin
authors: J
authors: Gong
authors: Yunfei
authors: Y
authors: Zhang
authors: John
authors: J
authors: Durfee
authors: Desheng
authors: D
authors: Weng
authors: Chunlei
authors: C
authors: Liu
authors: Shigeo
authors: S
authors: Koido
authors: Baizheng
authors: B
authors: Song
authors: Vasso
authors: V
authors: Apostolopoulos
authors: Stuart K
authors: SK
authors: Calderwood
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D045744:Cell Line, Tumor / Q000276:immunology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D016233:Immunotherapy, Active / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D050884:HSP72 Heat-Shock Proteins