title: Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.
abstract: The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2(-)/HLA-24(-)), carcinoembryonic antigen (CEA)(+), and MUC1(+) as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2(+) and/or HLA-A24(+)) and allogeneic COLM-6 resulted in MHC class I- and MHC class II-restricted proliferation of CD4(+) and CD8(+) T cells, high levels of IFN-gamma production in both CD4(+) and CD8(+) T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa, Chiba, Japan. shigeo_koido@jikei.ac.jp
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hara
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
authors.forename: Akira
authors.initials: A
authors.lastname: Torii
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Toyama
authors.forename: Hidejiro
authors.initials: H
authors.lastname: Kawahara
authors.forename: Michiaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Fujise
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
authors.forename: Jianlin
authors.initials: J
authors.lastname: Gong
authors.forename: Gotaro
authors.initials: G
authors.lastname: Toda
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009000:Monocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007376:Interleukin-2; D010455:Peptides; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma