title: Dendritic-tumor fusion cells derived heat shock protein70-peptide complex has enhanced immunogenicity.
abstract: Tumor-derived heat shock protein70-peptide complexes (HSP70.PC-Tu) have shown great promise in tumor immunotherapy due to numerous advantages. However, large-scale phase III clinical trials showed that the limited immunogenicity remained to be enhanced. In previous research, we demonstrated that heat shock protein 70-peptide complexes (HSP70.PC-Fc) derived from dendritic cell (DC)-tumor fusions exhibit enhanced immunogenicity compared with HSP70.PCs from tumor cells. However, the DCs used in our previous research were obtained from healthy donors and not from the patient population. In order to promote the clinical application of these complexes, HSP70.PC-Fc was prepared from patient-derived DC fused directly with patient-derived tumor cells in the current study. Our results showed that compared with HSP70.PC-Tu, HSP70.PC-Fc elicited much more powerful immune responses against the tumor from which the HSP70 was derived, including enhanced T cell activation, and CTL responses that were shown to be antigen specific and HLA restricted. Our results further indicated that the enhanced immunogenicity is related to the activation of CD4+ T cells and increased association with other heat shock proteins, such as HSP90. Therefore, the current study confirms the enhanced immunogenicity of HSP70.PC derived from DC-tumor fusions and may provide direct evidence promoting their future clinical use.
authors.affiliation: Department of Orthopaedic, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an, Shaanxi Province, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an, Shaanxi Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an, Shaanxi Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an, Shaanxi Province, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Changle Road, Xi'an, Shaanxi Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
mesh_terms: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology; D061986:MCF-7 Cells; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides