title: Human dendritic cells engineered to secrete interleukin-18 activate MAGE-A3-specific cytotoxic T lymphocytes in vitro.
abstract: Adoptive cell transfer (ACT) involves the administration of tumor specific cytotoxic T lymphocytes (CTLs) into a patient to kill cancer cells. Although a promising cancer therapy, limitations on the generation of activated CTLs have restricted ATC's clinical application. Interleukin-18 (IL-18) is an interferon-γ (IFN-γ) inducing factor that plays an important functional role in regulating CTLs. Here, we attempt to use dendritic cells (DCs) modified with a recombinant adenovirus encoding IL-18 (rAd/IL-18) to improve the generation of activated tumor-specific CTLs. These engineered DCs secrete IL-18, increase the expression of co-stimulatory molecules, and enhance the cytotoxic efficacy of melanoma antigen 3 (MAGE-A3)-specific CTLs in vitro. We show that stimulation of CTLs with rAd/IL-18-loaded DCs increases the specific lysis of MAGE-A3-expressing human breast cancer MCF-7 cells, and at the same time increases the production of activated MAGE-A3-specific CTLs. Our results indicate that transducing DCs with rAd/IL-18 increases both the maturation of DCs and the activation level of MAGE-A3-specific CTLs, greatly enhancing the cytotoxic efficacy of CTLs towards tumor cells.
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Fan
authors.forename: Mulin
authors.initials: M
authors.lastname: Ye
authors.forename: Bofu
authors.initials: B
authors.lastname: Xue
authors.forename: Yan
authors.initials: Y
authors.lastname: Ke
authors.forename: Chung Kai
authors.initials: CK
authors.lastname: Wong
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer; D000951:Antigens, Neoplasm / Q000276:immunology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology*; D019169:Jurkat Cells; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D020382:Interleukin-18; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins