PMID- 25792826 OWN - NLM STAT- MEDLINE DCOM- 20160516 LR - 20220318 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 10 DP - 2015 TI - Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer. PG - 1921-30 LID - 10.2147/IJN.S74204 [doi] AB - PURPOSE: Vaccines play important roles in antitumor biotherapy. Autophagy in tumor cells plays a critical role in depredating proteins, including tumor-specific antigens and tumor-associated antigens. We aimed to induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as a novel antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. MATERIALS AND METHODS: DRibbles were prepared and their morphological and autophagic properties characterized. Dendritic cells (DCs) generated from the bone marrow monocytes of mice were cocultured with DRibbles, then surface molecules of DCs and B cells, as well as apoptosis of DCs, were determined by flow cytometry. Meanwhile, functional properties of the DRibble-DCs were examined by mixed lymphocyte reactions and animal experiments. RESULTS: The diameter of autophagic nanoparticles with spherical and double-membrane structure was between 200 nm and 500 nm. DRibbles resulted in the upregulation of costimulatory molecules CD40 and CD86 as well as major histocompatibility complex (MHC)-I molecules on DCs, but not MHC-II. The expressions of CD40, CD80, and CD86 and that of MHC-II molecules on B cells were also upregulated. Moreover, suppression of tumor growth and lifetime prolongation was observed in DRibble-DC-vaccinated tumor-bearing mice. CONCLUSION: Our results demonstrate that naive T cells can be activated effectively by DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials. FAU - Su, Hang AU - Su H AD - Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China. FAU - Luo, Qiong AU - Luo Q AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China. FAU - Xie, Hao AU - Xie H AD - Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, People's Republic of China. FAU - Huang, Xiaofeng AU - Huang X AD - Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China. FAU - Ni, Yanhong AU - Ni Y AD - Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China. FAU - Mou, Yongbin AU - Mou Y AD - Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China. FAU - Hu, Qingang AU - Hu Q AD - Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China ; Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150310 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Cancer Vaccines) SB - IM MH - Animals MH - Autophagy/*immunology MH - *Cancer Vaccines MH - Cells, Cultured MH - Dendritic Cells/immunology MH - *Head and Neck Neoplasms/immunology/prevention & control MH - Mice PMC - PMC4364158 OTO - NOTNLM OT - antitumor immunity OT - autophagy OT - dendritic cells OT - head and neck cancer OT - nanoparticles EDAT- 2015/03/21 06:00 MHDA- 2016/05/18 06:00 PMCR- 2015/03/10 CRDT- 2015/03/21 06:00 PHST- 2015/03/21 06:00 [entrez] PHST- 2015/03/21 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] PHST- 2015/03/10 00:00 [pmc-release] AID - ijn-10-1921 [pii] AID - 10.2147/IJN.S74204 [doi] PST - epublish SO - Int J Nanomedicine. 2015 Mar 10;10:1921-30. doi: 10.2147/IJN.S74204. eCollection 2015.