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.
Highlights
Numerous preclinical and clinical studies have shown that tumor-derived heat shock proteinpeptide complexes (HSP.PC) can induce antitumor immune responses [1,2,3,4]
Our results show that HSP70.PC derived from dendritic cell (DC)-tumor fusion cells can elicit much more powerful antitumor immune responses against autologous tumor cells than those from tumor cells
After fusion with PEG and 3 days of culture, fusion efficiency was determined by dual color flow cytometric analysis of fusion cell expression of the DC marker HLA-DR and the tumor marker HER2/neu
Summary
Numerous preclinical and clinical studies have shown that tumor-derived heat shock proteinpeptide complexes (HSP.PC) can induce antitumor immune responses [1,2,3,4]. Vaccination with tumor derived GP96, HSP70 or HSP90 can induce protective immunity against the tumors challenge used as the source of the HSPs in animal studies[5,6]. Effective treatment including reducing of tumor burden and inhibition of metastasis can be induced [7,8]. The results from clinical trials (including phase III) proved effective tumor-specific. DC/Tumor Fusion Cells Derived HSP70.PC Has Enhanced Immunogenicity
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