title: Induction of antigen-specific cytotoxic T lymphocytes by fusion cells generated from allogeneic plasmacytoid dendritic and tumor cells.
abstract: Previous work has demonstrated that fusion cells generated from autologous monocyte-derived dendritic cells (MoDCs) and whole tumor cells induce efficient antigen-specific cytotoxic T lymphocytes. A major limitation to the use of this strategy is the availability of adequate amounts of autologous tumor cells. Moreover, MoDCs from cancer patients are often defective in their antigen-processing and presentation machinery. In this study, two types of allogeneic cells, a leukemia plasmacytoid dendritic cell (pDC) line (PMDC05) and pancreatic cancer cell lines (PANC-1 or MIA PaCa-2), were fused instead of autologous MoDCs and tumor cells. We created four types of pDC/tumor fusion cells by alternating fusion partners and treating with lipopolysaccharide (LPS): i) PMDC05 fused with PANC-1 (pDC/PANC-1), ii) PMDC05 fused with MIA PaCa-2 (pDC/MIA PaCa-2), iii) LPS-stimulated pDC/PANC-1 (LPS-pDC/PANC-1) and iv) LPS-stimulated pDC/MIA PaCa-2 (LPS-pDC/MIA PaCa-2) and examined their antitumor immune responses. The LPS-pDC/tumor cell fusions were the most active, as demonstrated by their: i) upregulated expression of HLA-DR and CD86 on a per-fusion-cell basis, ii) increased production of IL-12p70, iii) generation of a higher percentage of IFN-γ-producing CD4⁺ and CD8⁺ T cells and iv) augmented induction of MUC1-specific CD8⁺ T cells that lyse target tumor cells. This study provides the first evidence for an in vitro induction of antigen-specific cytotoxic T lymphocytes by LPS-stimulated fusion cells generated from leukemia plasmacytoid DCs and tumor cells and suggests that this strategy has potential applicability to the field of adoptive immunotherapy.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.affiliation: Department of Oncology, Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
authors.affiliation: Department of Oncology, Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kan
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takakura
authors.affiliation: Institute of Clinical Medicine and Research, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Namiki
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Zensho
authors.initials: Z
authors.lastname: Ito
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Arihiro
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Gong
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Chiba 277-8564, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D018396:Mucin-1 / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C060192:MUC1 protein, human; D018396:Mucin-1