PMID- 30027430 OWN - NLM STAT- MEDLINE DCOM- 20190312 LR - 20240407 IS - 1878-7479 (Electronic) IS - 1933-7213 (Print) IS - 1878-7479 (Linking) VI - 15 IP - 4 DP - 2018 Oct TI - A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model. PG - 1127-1138 LID - 10.1007/s13311-018-0650-3 [doi] AB - Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261(CMV-IE)-implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas. FAU - Kim, Julius W AU - Kim JW AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Kane, J Robert AU - Kane JR AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Panek, Wojciech K AU - Panek WK AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Young, Jacob S AU - Young JS AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Rashidi, Aida AU - Rashidi A AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Yu, Dou AU - Yu D AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Kanojia, Deepak AU - Kanojia D AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Hasan, Tanwir AU - Hasan T AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Miska, Jason AU - Miska J AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Gomez-Lim, Miguel A AU - Gomez-Lim MA AD - Departamento de Ingenieria Genetica, CINVESTAV Irapuato, Km 9.6 Libramiento Norte Carretera Irapuato-Leon, 36821, Irapuato, Guanajuato, Mexico. FAU - Ulasov, Ilya V AU - Ulasov IV AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Balyasnikova, Irina V AU - Balyasnikova IV AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Ahmed, Atique U AU - Ahmed AU AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Wainwright, Derek A AU - Wainwright DA AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. FAU - Lesniak, Maciej S AU - Lesniak MS AD - Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. maciej.lesniak@northwestern.edu. LA - eng GR - F32 NS073366/NS/NINDS NIH HHS/United States GR - R00 NS082381/NS/NINDS NIH HHS/United States GR - R01 NS093903/NS/NINDS NIH HHS/United States GR - R35CA197725/NH/NIH HHS/United States GR - R01NS093903/NH/NIH HHS/United States GR - K99 NS082381/NS/NINDS NIH HHS/United States GR - R01CA122930/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Neurotherapeutics JT - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics JID - 101290381 RN - 0 (Antigens, CD) RN - 0 (Antigens, Neoplasm) RN - 0 (DEC-205 receptor) RN - 0 (Lectins, C-Type) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (Receptors, Cell Surface) SB - IM MH - Adaptive Immunity/*genetics MH - Adenoviridae/genetics MH - Analysis of Variance MH - Animals MH - Antigens, CD/*metabolism MH - Antigens, Neoplasm/*metabolism MH - *Brain Neoplasms/immunology/pathology/therapy MH - Dendritic Cells/*immunology/virology MH - Disease Models, Animal MH - Genetic Vectors/metabolism MH - *Glioma/immunology/pathology/therapy MH - HEK293 Cells MH - Humans MH - Lectins, C-Type/*metabolism MH - Lymph Nodes/cytology MH - Mice MH - Minor Histocompatibility Antigens/*metabolism MH - Receptors, Cell Surface/*metabolism MH - Spleen/cytology MH - Transduction, Genetic MH - Transfection MH - Xenograft Model Antitumor Assays PMC - PMC6277295 OTO - NOTNLM OT - adenovirus OT - cytomegalovirus OT - dendritic cells OT - glioblastoma OT - vaccine EDAT- 2018/07/22 06:00 MHDA- 2019/03/13 06:00 PMCR- 2019/10/01 CRDT- 2018/07/21 06:00 PHST- 2018/07/22 06:00 [pubmed] PHST- 2019/03/13 06:00 [medline] PHST- 2018/07/21 06:00 [entrez] PHST- 2019/10/01 00:00 [pmc-release] AID - S1878-7479(23)01037-1 [pii] AID - 650 [pii] AID - 10.1007/s13311-018-0650-3 [doi] PST - ppublish SO - Neurotherapeutics. 2018 Oct;15(4):1127-1138. doi: 10.1007/s13311-018-0650-3.