PMID- 22490235 OWN - NLM STAT- MEDLINE DCOM- 20121009 LR - 20120607 IS - 1532-4311 (Electronic) IS - 0882-0139 (Linking) VI - 41 IP - 5 DP - 2012 TI - Human dendritic cells engineered to secrete interleukin-18 activate MAGE-A3-specific cytotoxic T lymphocytes in vitro. PG - 469-83 LID - 10.3109/08820139.2012.664225 [doi] AB - 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-gamma (IFN-gamma) 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. FAU - Fan, Xueling AU - Fan X AD - Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. FAU - Ye, Mulin AU - Ye M FAU - Xue, Bofu AU - Xue B FAU - Ke, Yan AU - Ke Y FAU - Wong, Chung Kai AU - Wong CK FAU - Xie, Yong AU - Xie Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120410 PL - England TA - Immunol Invest JT - Immunological investigations JID - 8504629 RN - 0 (Antigens, Neoplasm) RN - 0 (Interleukin-18) RN - 0 (MAGEA3 protein, human) RN - 0 (Neoplasm Proteins) SB - IM MH - Adenoviridae/genetics MH - Adoptive Transfer MH - Antigens, Neoplasm/*immunology MH - Cell Differentiation MH - Cell Line, Tumor MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Interleukin-18/*immunology MH - Jurkat Cells MH - Neoplasm Proteins/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology EDAT- 2012/04/12 06:00 MHDA- 2012/10/10 06:00 CRDT- 2012/04/12 06:00 PHST- 2012/04/12 06:00 [entrez] PHST- 2012/04/12 06:00 [pubmed] PHST- 2012/10/10 06:00 [medline] AID - 10.3109/08820139.2012.664225 [doi] PST - ppublish SO - Immunol Invest. 2012;41(5):469-83. doi: 10.3109/08820139.2012.664225. Epub 2012 Apr 10.