Optimization of the concentration of autologous serum for generation of leukemic dendritic cells from acute myeloid leukemic cells for clinical immunotherapy.
Clinical application of immunotherapy for acute myeloid leukemia (AML) requires the efficient induction of dendritic cells (DCs) from AML blast cells using in vitro culture. We examined the effect of autologous serum on the properties of leukemic DCs derived from leukemic cells of AML patients by culture in AIM-V medium with GM-CSF, IL-4, TNF-alpha, and 0, 2, 5, or 10% human autologous serum. The expressions of CD80, CD83, CD86, and HLA-DR were upregulated under all culture conditions; however, 10% autologous serum induced the highest expression levels of several molecules. The capacity of leukemic DCs to stimulate allogeneic T cells increased with increasing serum concentration. Stimulation of autologous CD3(+) T cells with leukemic DCs grown in the presence of various concentrations of autologous serum resulted in induction of more IFN-gamma-secreting cells than was the case for unprimed CD3(+) T cells. Leukemic DCs cultured with 10% autologous serum induced the highest numbers of IFN-gamma-secreting cells and CD8(+)CD56(+) T cells from autologous T cells. These results suggest that culture of AML blast cells in the presence of autologous serum could be used to generate leukemic DCs for immunotherapy against AML. The highest serum concentration appeared optimal for generating the most potent leukemic DCs.
Choi
Bo-Hwa
BH
Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
Kang
Hyun-Kyu
HK
Park
Jung-Sun
JS
Kim
Sang-Ki
SK
Pham
Than-Nhan Nguyen
TN
Zhu
Xiao-Wei
XW
Cho
Duck
D
Nam
Jong-Hee
JH
Chung
Ik-Joo
IJ
Kim
Young-Jin
YJ
Rhee
Joon-Haeng
JH
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D044967:Serum; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen