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Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.
Clin Cancer Res 2005; 11(21):7891-900CC

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+Show Affiliations

Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa, Chiba, Japan. shigeo_koido@jikei.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16278414

Citation

Koido, Shigeo, et al. "Dendritic Cells Fused With Allogeneic Colorectal Cancer Cell Line Present Multiple Colorectal Cancer-specific Antigens and Induce Antitumor Immunity Against Autologous Tumor Cells." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 21, 2005, pp. 7891-900.
Koido S, Hara E, Homma S, et al. Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells. Clin Cancer Res. 2005;11(21):7891-900.
Koido, S., Hara, E., Homma, S., Torii, A., Toyama, Y., Kawahara, H., ... Toda, G. (2005). Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(21), pp. 7891-900.
Koido S, et al. Dendritic Cells Fused With Allogeneic Colorectal Cancer Cell Line Present Multiple Colorectal Cancer-specific Antigens and Induce Antitumor Immunity Against Autologous Tumor Cells. Clin Cancer Res. 2005 Nov 1;11(21):7891-900. PubMed PMID: 16278414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells. AU - Koido,Shigeo, AU - Hara,Eiichi, AU - Homma,Sadamu, AU - Torii,Akira, AU - Toyama,Yoichi, AU - Kawahara,Hidejiro, AU - Watanabe,Michiaki, AU - Yanaga,Katsuhiko, AU - Fujise,Kiyotaka, AU - Tajiri,Hisao, AU - Gong,Jianlin, AU - Toda,Gotaro, PY - 2005/11/10/pubmed PY - 2006/4/6/medline PY - 2005/11/10/entrez SP - 7891 EP - 900 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 11 IS - 21 N2 - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16278414/Dendritic_cells_fused_with_allogeneic_colorectal_cancer_cell_line_present_multiple_colorectal_cancer_specific_antigens_and_induce_antitumor_immunity_against_autologous_tumor_cells_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16278414 DB - PRIME DP - Unbound Medicine ER -