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Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL

Authors
 Jing-Hua Huang  ;  Song-Nan Zhang  ;  Kyung-Ju Choi  ;  Il-Kyu Choi  ;  Joo-Hang Kim  ;  Mingul Lee  ;  Hoguen Kim  ;  Chae-Ok Yun 
Citation
 MOLECULAR THERAPY, Vol.18(2) : 264-274, 2010 
Journal Title
 MOLECULAR THERAPY 
ISSN
 1525-0016 
Issue Date
2010
MeSH
4-1BB Ligand/genetics ; 4-1BB Ligand/immunology* ; 4-1BB Ligand/physiology ; Adenoviridae/genetics ; Adenoviridae/physiology* ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Dendritic Cells/cytology ; Dendritic Cells/physiology* ; Humans ; In Vitro Techniques ; Interleukin-12/genetics ; Interleukin-12/immunology* ; Interleukin-12/physiology ; Melanoma/immunology* ; Melanoma/therapy* ; Mice ; Mice, Inbred C57BL ; Oncolytic Viruses/genetics ; Oncolytic Viruses/physiology*
Abstract
Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-gamma levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-gamma-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.
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DOI
10.1038/mt.2009.205
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Kim, Ho Keun(김호근)
Yun, Chae Ok(윤채옥)
Lee, Min Geol(이민걸) ORCID logo https://orcid.org/0000-0001-7040-5335
Zhang, Song Nan(장송남)
Choi, Kyung Ju(최경주)
Choi, Il Kyu(최일규)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100657
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