Dendritic-Tumor Fusion Cells Derived Heat Shock Protein70-Peptide Complex Has Enhanced Immunogenicity
نویسندگان
چکیده
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.
منابع مشابه
Enhanced antitumor immunity of nanoliposome-encapsulated heat shock protein 70 peptide complex derived from dendritic tumor fusion cells
Tumor-derived heat shock proteins peptide complex (HSP.PC-Tu) has been regarded as a promising antitumor agent. However, inadequate immunogenicity and low bioavailability limit the clinical uses of this agent. In a previous study, we first produced an improved HSP70.PC-based vaccine purified from dendritic cell (DC)-tumor fusion cells (HSP70.PC-Fc) which had increased immunogenicity due to enha...
متن کاملA heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use.
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 ce...
متن کاملCell-Tumor Fusion Cells Dendritic Protein 70 Peptide Complexes from Enhanced Immunogenicity of Heat Shock
متن کامل
Prokaryotic Expression of Influenza A virus Nucleoprotein Fused to Mycobacterial Heat Shock Protein70
Background and Aims: The novel approaches in influenza vaccination have targeted more conserved viral proteins such as nucleoprotein (NP) to provide cross protection against all serotypes of influenza A viruses. Influenza specific cytotoxic T lymphocytes (CTL) are able to lyse influenza-infected cells by recognition of NP, the major target molecule in virus for CTL responses. On the other hand,...
متن کاملA new purification method for enhancing the immunogenicity of heat shock protein 70-peptide complexes
When purified from a tumor, certain heat shock protein 70 (HSP70)-peptide complexes (PCs) can function as effective vaccines against the tumor from which the complexes were isolated. The immunogenic mechanisms of HSP70 preparations imply that tumor-derived HSP70-PCs exhibit antigens associated with antigen-presenting cells such as dendritic cells ...
متن کامل