Journal of Molecular Medicine

, Volume 84, Issue 12, pp 1067–1076

Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8+ CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells

  • Shengming Dai
  • Xiangyang Zhou
  • Baomei Wang
  • Qingqing Wang
  • Yangxin Fu
  • Taoyong Chen
  • Tao Wan
  • Yizhi Yu
  • Xuetao Cao
Original Article

DOI: 10.1007/s00109-006-0102-0

Cite this article as:
Dai, S., Zhou, X., Wang, B. et al. J Mol Med (2006) 84: 1067. doi:10.1007/s00109-006-0102-0

Abstract

Dendritic cells (DC)-derived or tumor-derived exosomes are a population of nanometer sized membrane vesicles that can induce specific anti-tumor immunity. However, the immunogenic potential and efficiency of exosomes-based tumor vaccine are not satisfactory enough to achieve a curative effect in clinical trials. In this article we investigated whether IL-18 genetic modification of tumor cells can increase the efficacy of exosomes derived from IL-18 gene-modified tumor cells. We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells. We found that Exo/IL-18 naturally contain CEA and bioactive IL-18. Moreover, Exo-IL-18 are potent in chemoattracting DC and T cells, enhancing the proliferation and Th1 cytokine release of PBMC, and promoting the phenotypic and functional maturation of DC. Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8+ CTL from the PBMC of HLA-A*0201 CEA+ cancer patients in vitro. In almost all of these experiments, Exo/IL-18 show more potent functions than the conventionally prepared exosomes derived from parent tumor cells without IL-18 gene modification. Our findings suggest that Exo/IL-18 has more potent capability to induce specific anti-tumor immunity, and our strategy of IL-18 modification of exosomes is a feasible approach to develop exosomes-based tumor vaccines.

Keywords

Exosomes CEA IL-18 Dendritic cells CTL 

Abbreviations

DC

dendritic cells

CEA

carcinoembryonic antigen

AdhIL-18

recombinant adenovirus encoding human IL-18

Exo

exosomes derived from tumor cells

Exo/IL-18

exosomes derived from AdhIL-18-transfected tumor cells

MLR

mixed lymphocyte reaction

CTL

cytotoxic T lymphocytes

MOI

multiplicity of infection

PBMC

peripheral blood mononuclear cells

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Shengming Dai
    • 1
    • 2
  • Xiangyang Zhou
    • 2
  • Baomei Wang
    • 2
  • Qingqing Wang
    • 1
  • Yangxin Fu
    • 1
  • Taoyong Chen
    • 2
  • Tao Wan
    • 2
  • Yizhi Yu
    • 2
  • Xuetao Cao
    • 1
    • 2
  1. 1.Institute of ImmunologyZhejiang UniversityHangzhouPeople’s Republic of China
  2. 2.Institute of Immunology and State Key Laboratory of Medical ImmunologySecond Military Medical UniversityShanghaiPeople’s Republic of China

Personalised recommendations