Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1831–1843

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

DOI: 10.1007/s00262-007-0327-y

Cite this article as:
Xue, G., Liu, R., Li, Y. et al. Cancer Immunol Immunother (2007) 56: 1831. doi:10.1007/s00262-007-0327-y

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 cellsCytokinesChemokinesTumor immunologyGene 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

Supplementary material

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