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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 exosomesbased tumor vaccines.

Original languageEnglish (US)
Pages (from-to)1067-1076
Number of pages10
JournalJournal of Molecular Medicine
Volume84
Issue number12
DOIs
StatePublished - Dec 1 2006

Fingerprint

Exosomes
Interleukin-18
Carcinoembryonic Antigen
Dendritic Cells
Genes
Neoplasms
Cancer Vaccines
HLA-A*02:01 antigen
Immunity
Adenoviridae

Keywords

  • CEA
  • CTL
  • Dendritic cells
  • Exosomes
  • IL-18

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

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. / Dai, Shengming; Zhou, Xiangyang; Wang, Baomei; Wang, Qingqing; Fu, Yangxin; Chen, Taoyong; Wan, Tao; Yu, Yizhi; Cao, Xuetao.

In: Journal of Molecular Medicine, Vol. 84, No. 12, 01.12.2006, p. 1067-1076.

Research output: Contribution to journalArticle

Dai, Shengming ; Zhou, Xiangyang ; Wang, Baomei ; Wang, Qingqing ; Fu, Yangxin ; Chen, Taoyong ; Wan, Tao ; Yu, Yizhi ; Cao, Xuetao. / 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. In: Journal of Molecular Medicine. 2006 ; Vol. 84, No. 12. pp. 1067-1076.
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AU - Zhou, Xiangyang

AU - Wang, Baomei

AU - Wang, Qingqing

AU - Fu, Yangxin

AU - Chen, Taoyong

AU - Wan, Tao

AU - Yu, Yizhi

AU - Cao, Xuetao

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AB - 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 exosomesbased tumor vaccines.

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