Induction of myeloma-specific cytotoxic T lymphocytes ex vivo by CD40-activated B cells loaded with myeloma tumor antigens.
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.
Kim
Sang-Ki
SK
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
Nguyen Pham
Thanh-Nhan
TN
Nguyen Hoang
Tuyet Minh
TM
Kang
Hyun-Kyu
HK
Jin
Chun-Ji
CJ
Nam
Jong-Hee
JH
Chung
Sang-Young
SY
Choi
So-Jin-Na
SJ
Yang
Deok-Hwan
DH
Kim
Yeo-Kyeoung
YK
Chung
Ik-Joo
IJ
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
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
D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D007328:Insulin; D008222:Lymphokines; D014168:Transferrin; D015847:Interleukin-4; D016572:Cyclosporine