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.
| Original language | English |
|---|---|
| Pages (from-to) | 889-898 |
| Number of pages | 10 |
| Journal | Journal of Gene Medicine |
| Volume | 11 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2009 Dec 28 |
Fingerprint
Keywords
- Cancer vaccine
- Chemokine
- Dendritic cell
- Immunotherapy
- IP-10
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Molecular Medicine
- Genetics(clinical)
- Drug Discovery
Cite this
Modification of dendritic cells with interferon-γ -inducible protein-10 gene to enhance vaccine potency. / Kang, Tae Heung; Bae, Hyun Cheol; Kim, Seok Ho; Seo, Soo-Hong; Son, Sang Wook; Choi, Eun Young; Seong, Seung Yong; Kim, Tae Woo.
In: Journal of Gene Medicine, Vol. 11, No. 10, 28.12.2009, p. 889-898.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modification of dendritic cells with interferon-γ -inducible protein-10 gene to enhance vaccine potency
AU - Kang, Tae Heung
AU - Bae, Hyun Cheol
AU - Kim, Seok Ho
AU - Seo, Soo-Hong
AU - Son, Sang Wook
AU - Choi, Eun Young
AU - Seong, Seung Yong
AU - Kim, Tae Woo
PY - 2009/12/28
Y1 - 2009/12/28
N2 - 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.
AB - 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.
KW - Cancer vaccine
KW - Chemokine
KW - Dendritic cell
KW - Immunotherapy
KW - IP-10
UR - http://www.scopus.com/inward/record.url?scp=72449175976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72449175976&partnerID=8YFLogxK
U2 - 10.1002/jgm.1371
DO - 10.1002/jgm.1371
M3 - Article
C2 - 19618483
AN - SCOPUS:72449175976
VL - 11
SP - 889
EP - 898
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
SN - 1099-498X
IS - 10
ER -