title: Induction of myeloma-specific cytotoxic T lymphocytes ex vivo by CD40-activated B cells loaded with myeloma tumor antigens.
abstract: We investigated to establish CD40-activated B cells (CD40-B cells) as alternative antigen-presenting cells (APCs) for the induction of myeloma-specific cytotoxic T lymphocytes (CTLs). To generate CD40-B cells, peripheral blood mononuclear cells were co-cultured with CD40L-transfected J558 cells in the presence of IL-4, insulin, transferrin, and cyclosporine for 14 days, and pulsed with myeloma lysates. The CD40-B cells consistently expressed high levels of CD80, CD86, CD54, CCR7, and HLA-DR. The CD40-B cells produced IL-12, IFN-gamma, and IL-6 during the culture period, but not IL-10. In addition, the CD40-B cells showed potent allogeneic T-cell stimulatory capacities that depended on the dose ratio and had the potential to polarize naïve T cells into Th1 subsets. The CD40-B cells loaded with tumor lysates induced strong target-specific CTLs, based on large numbers of IFN-gamma secreting cells and higher cytotoxic activity against target cells compared to the CD40-B cells without the tumor lysates. These results suggest that CD40-B cells loaded with myeloma lysates might provide alternative APCs for cellular immunotherapy in patients with myeloma.
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
authors.forename: Sang-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Thanh-Nhan
authors.initials: TN
authors.lastname: Nguyen Pham
authors.forename: Tuyet Minh
authors.initials: TM
authors.lastname: Nguyen Hoang
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Kang
authors.forename: Chun-Ji
authors.initials: CJ
authors.lastname: Jin
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Nam
authors.forename: Sang-Young
authors.initials: SY
authors.lastname: Chung
authors.forename: So-Jin-Na
authors.initials: SJ
authors.lastname: Choi
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007328:Insulin / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D007328:Insulin; D008222:Lymphokines; D014168:Transferrin; D015847:Interleukin-4; D016572:Cyclosporine