Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1831–1843 | Cite as

Dendritic cells modified with 6Ckine/IFNγ fusion gene induce specific cytotoxic T lymphocytes in vitro

  • Gang Xue
  • Ran-yi Liu
  • Yan Li
  • Ying Cheng
  • Zhi-hui Liang
  • Jiang-xue Wu
  • Mu-sheng Zeng
  • Fu-zhou Tian
  • Wenlin Huang
Original Article

Abstract

Backgroud and objective

Dendritic cells play an important role in initiation and regulation of immune responses. Previous studies demonstrated that intratumoral administration of 6Ckine-modified DCs enhanced local and systemic antitumor effects. Herein we report the investigation of the specific CTL responses elicited by adenoviral 6Ckine/IFNγ fusion gene-modified DCs in vitro.

Methods

Human monocyte-derived DCs were modified with an adenoviral vector encoding 6Ckine/IFNγ fusion protein (Ad-6Ckine/IFNγ), and then investigated the effect of 6Ckine/IFNγ fusion protein on the maturation, cytokine and chemokine secretion of DCs, and their activities of recruiting and activating T cells in vitro were investigated.

Results

6Ckine/IFNγ fusion protein induced DC maturation characterized with the upregulation of CD83 and CCR7. And it up-regulated the expression of RANTES and IL-12p70, down-regulated that of IL-10 in DCs. Additionally, 6Ckine/IFNγ markedly increased DC’s recruiting ability for naive T cells, benefiting from the enhanced expression of chemokines 6Ckine and RANTES in DCs. Fusion gene-modified DCs significantly promoted the proliferation of autologous T cells, induced Th1 differentiation by upregulating the expression of IL-2 and T-bet in T cells, and increased specific cytotoxicity of CTLs against specific tumor cells, HepG2 or LoVo cells, respectively.

Conclusion

Combining the effects of 6Ckine and IFNγ, Ad-6Ckine/IFNγ modified DCs induced enhanced CTL responses in vitro, which indicated that Ad-6Ckine/IFNγ modified DCs might be used as an adjuvant to trigger an effective antitumor immune response.

Keywords

Dendritic cells Cytokines Chemokines Tumor immunology Gene therapy 

Abbreviations

Ad-6Ckine/IFNγ

Recombinant adenovirus carrying 6Ckine/IFNγ fusion gene

Ad-6Ckine

Recombinant adenoviruses carrying 6Ckine gene

Ad-IFNγ

Recombinant adenoviruses carrying IFNγ gene

Ad-LacZ

Recombinant adenoviruses carrying β-galactosidase gene

Ad-GFP

Recombinant adenoviruses carrying green fluorescent protein gene

TAAs

Tumor-associated antigens

Ad-6Ckine-DC

DC transfected with Ad-6Ckine

Ad-6Ckine/IFNγ-DC

DC transfected with Ad-6Ckine/IFNγ

NTDC

Non-transfected DC

Ad-IFNγ-DC

DC transfected with Ad-IFNγ

Ad-LacZ-DC

DC transfected with Ad-LacZ

LDH

Lactate dehydrogenase

NICPBP

National Institute for the Control of Pharmaceutical and Biological Products

Notes

Acknowledgments

This study was supported by the grants from National Basic Research Program of China (No.2004CB518801), Research & Development Fund of Guangdong Provine (No.2003A10902), Natural Science Foundation of Guangdong Province (No.021810), Research & Development Fund of Guangzhou City (No.2004Z3-E4011), and Medical Science Grant from Guangdong Province (No.B2002050). We thank Miao-la Ke, Jie-min Chen, Ying-hui Zhu and Xia Xiao (Sun Yat-sen University) for their technical assistance. We thank Dr. Changyou Wu, Dr. Li-min Zeng, and Dr. Qiang Liu (Sun Yat-sen University) for their review of this article. We also thank Ying-jun Ji (Doublle Bioproduct Inc.) and Yin Duan (Simon Fraser University) for their linguistic help in the preparation of this manuscript.

Supplementary material

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Gang Xue
    • 3
  • Ran-yi Liu
    • 1
  • Yan Li
    • 1
  • Ying Cheng
    • 4
  • Zhi-hui Liang
    • 1
  • Jiang-xue Wu
    • 1
  • Mu-sheng Zeng
    • 1
  • Fu-zhou Tian
    • 3
  • Wenlin Huang
    • 1
    • 2
  1. 1.State Key Laboratory of Oncology in South China, Room 619, Cancer CenterSun Yat-sen UniversityGuangzhouChina
  2. 2.Beijing Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  3. 3.Department of General SurgeryChengdu Army General HospitalChengduChina
  4. 4.Department of EndocrinologyChengdu Army General HospitalChengduChina

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