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Neurotherapeutics. 2018 Oct;15(4):1127-1138. doi: 10.1007/s13311-018-0650-3.

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.

Author information

1
Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA.
2
Departamento de Ingeniería Genética, CINVESTAV Irapuato, Km 9.6 Libramiento Norte Carretera Irapuato-León, 36821, Irapuato, Guanajuato, Mexico.
3
Department of Neurological Surgery, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, Illinois, 60611, USA. maciej.lesniak@northwestern.edu.

Abstract

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 GL261CMV-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.

KEYWORDS:

adenovirus; cytomegalovirus; dendritic cells; glioblastoma; vaccine

PMID:
30027430
PMCID:
PMC6277295
DOI:
10.1007/s13311-018-0650-3
[Indexed for MEDLINE]
Free PMC Article

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