Modification of dendritic cells with interferon-gamma-inducible protein-10 gene to enhance vaccine potency
- Authors
- Kang, Tae Heung; Bae, Hyun Cheol; Kim, Seok-Ho; Seo, Su Hong; Son, Sang Wook; Choi, Eun Young; Seong, Seung-Yong; Kim, Tae Woo
- Issue Date
- 10월-2009
- Publisher
- WILEY
- Keywords
- IP-10; dendritic cell; cancer vaccine; immunotherapy; chemokine
- Citation
- JOURNAL OF GENE MEDICINE, v.11, no.10, pp.889 - 898
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF GENE MEDICINE
- Volume
- 11
- Number
- 10
- Start Page
- 889
- End Page
- 898
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/119199
- DOI
- 10.1002/jgm.1371
- ISSN
- 1099-498X
- Abstract
- Background Dendritic cell (DC)-based vaccines have become a promising modality in cancer immunotherapy. However, their ability to initiate tumor antigen-specific T cell immunity is limited in various negative-feedback mechanisms. The rapid down-regulation of chemokines, such as the interferon inducible protein of 10 kDa (IP-10), which chemoattracts activated antigen-specific CD8(+) T cells, would represent negative-feedback regulation. Therefore, we attempted to improve DC vaccine potency by introducing the IP-10 gene retrovirally aiming to replenish the chemoattractive activity of DCs. Methods We introduced IP-10 gene into DC2.4 cells, referred to as DC-IP10, using a retroviral system. Nonsecretable mIP-10-expressing DCs (DC-mIP10) were also prepared to evaluate the effects of secretion in IP-10-mediated modulation of DC biology. Additionally, in vitro and in vivo activation of antigen-specific T lymphocytes and in vivo anti-tumor effects induced by DC-IP10 or DC-mIP10 were determined. Results The modification of DC2.4 cells with the IP-10 gene resulted in the secretion of functionally chemoattractive IP-10 and, unexpectedly, a significant up-regulation of surface expression in co-stimulatory molecules, such as CD40 and CD80, compared to that of DCs with vector control (DC-no insert). DC-mIP10 also displayed the partially matured phenotypes but failed to recruit antigen-specific T cells in an in vitro cell culture system. Consistently, DC-IP10 generated more tumor antigen-specific CD8+ T cells and stronger anti-tumor effects in vaccinated mice than did control DCs and DC-mIP10. Conclusions The results obtained provide the groundwork for a future clinical translation of the chemokine-based genetic modification of DCs to increase their vaccine potency. Copyright (C) 2009 John Wiley & Sons, Ltd.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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