Yongxiang Yi1, Jianbo Han1, Liang Zhao1, Chunying Wang1, Yuan Fang1, Qiang Wei1, Liang Hu1, Junmao Liu1, Yufeng Zhang1, Lili Wang1. 1. 1 Department of Hepatobiliary Surgery, the Second Hospital of Nanjing, Affiliated to Southeast University, Nanjing 210003, China ; 2 Department of Hepatic Internal Medicine, Xuzhou Hospital for Infectious Diseases, Xuzhou 221004, China ; 3 Department of Immunotherapy, 4 Department of Interventional Ultrasound, the Second Hospital of Nanjing, Affiliated to Southeast University, Nanjing 210003, China.
Abstract
BACKGROUND: To induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. METHODS: Dendritic cells (DCs) generated from peripheral blood mononuclear cell (PBMC) of hepatocellular carcinoma (HCC) patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. RESULTS: DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay (ELISA) showed that IFN-γ levels after vaccination increased than before in most patients, but CD8+ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ were detected in the CD8+ cells than CD4+ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8+ T cell responses, supporting it as a tumor vaccine candidate. CONCLUSIONS: Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.
BACKGROUND: To induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. METHODS: Dendritic cells (DCs) generated from peripheral blood mononuclear cell (PBMC) of hepatocellular carcinoma (HCC) patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. RESULTS: DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay (ELISA) showed that IFN-γ levels after vaccination increased than before in most patients, but CD8+ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ were detected in the CD8+ cells than CD4+ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8+ T cell responses, supporting it as a tumor vaccine candidate. CONCLUSIONS: Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.
Authors: Hiroyuki Saiga; Natalie Nieuwenhuizen; Martin Gengenbacher; Anne-Britta Koehler; Stefanie Schuerer; Pedro Moura-Alves; Ina Wagner; Hans-Joachim Mollenkopf; Anca Dorhoi; Stefan H E Kaufmann Journal: J Infect Dis Date: 2014-12-11 Impact factor: 5.226
Authors: Michael I Koukourakis; Dimitra Kalamida; Alexandra Giatromanolaki; Christos E Zois; Efthimios Sivridis; Stamatia Pouliliou; Achilleas Mitrakas; Kevin C Gatter; Adrian L Harris Journal: PLoS One Date: 2015-09-17 Impact factor: 3.240