Dendritic Cell Based Cancer Vaccines Using Adenovirally Mediated Expression of the HER-2/neu gene and Apoptotic Tumor Cells Expressing Heat Shock Protein 70
In another study, we examined the use of a DC-based cancer vaccine involving the phagocytosis of apoptotic tumor cells expressing heat shock protein 70 (HSP70). The dual role of HSP70, as an antigenic peptide chaperone and danger signal, makes it especially important in DC-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/HSP tumor cells expressing HSP70 on DC maturation, T cell stimulation and overall vaccine efficacy. We found that DC with phagocytosis of MCA/HSP in the early phase of apoptosis expressed more peptide-major histocompatibility class (pMHC) I complexes, stimulated stronger cytotoxic T lymphocytes (CTL) responses and induced greater immune protection against MCA tumor cell challenge, compared to mice immunized with DC that phagocytosed MCA/HSP cells in the late phase of apoptosis. Taken together, our data demonstrated that HSP70 expression on apoptotic tumor cells stimulated DC maturation and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor-specific CTL responses and immunity than DC with phagocytosis of apoptotic tumor cells in late phase of apoptosis.
Overall, we have examined variations in designing DC-based cancer vaccines in two completely different model systems. Taken together, our results may have an important impact in designing DC-based antitumor vaccines.
Advisor:Xiang, Jim; Sharma, Rajendra K.; Saxena, Anurag; Sami, Amer; Qureshi, Mabood; Bathe, Oliver; Krahn, John
School:University of Saskatchewan
School Location:Canada - Saskatchewan
Source Type:Master's Thesis
Keywords:replication deficient adenovirus cancer vaccine breast dendritic cell her 2 neu apoptosis heat shock protein 70
Date of Publication:08/28/2006