Induction of multiple myeloma-specific cytotoxic T lymphocyte stimulation by dendritic cell pulsing with purified and optimized myeloma cell lysates.
We investigated the possibility of immunotherapy for multiple myeloma (MM) using myeloma-specific cytotoxic T lymphocytes (CTLs) that were stimulated in vitro by dendritic cells (DCs) pulsing with purified and optimized myeloma lysates. CD14(+) cells were cultured in the presence of GM-CSF and IL-4. On day 6, the immature DCs were pulsed with the purified myeloma cell lysates, and then maturation of the DCs was induced by the addition of a cytokine cocktail. There were no differences in the phenotypic expressions of mature DCs that were generated by pulsing with CD138(+) cell lysates or total cell lysates. In optimization of the concentration of myeloma lysates, DCs pulsed with 10 microg/mL of myeloma lysate had greater allogeneic T-cell stimulatory capacities than those pulsed with higher concentrations of myeloma lysates. The CTL lines generated by DCs pulsed with myeloma lysates demonstrated potent cytotoxic activities against autologous target cells, but not against HLA-A2(-) cell lines or K562 cell lines. The DCs pulsed with myeloma lysates demonstrated a higher stimulatory capacity for autologous CTL compared with mature nonpulsed DCs. These results suggested that the DCs pulsed with purified and optimized myeloma cell lysates could generate potent myeloma-specific CTLs for approaches in MM.
Lee
Je-Jung
JJ
Clinical Vaccine R&D Center, Chonnam National University, Hwasun, Jeonnam, Korea. ijchung@chonnam.ac.kr
Choi
Bo-Hwa
BH
Kang
Hyun-Kyu
HK
Park
Myong-Suk
MS
Park
Jung-Sun
JS
Kim
Sang-Ki
SK
Pham
Thanh-Nhan Nguyen
TN
Cho
Duck
D
Nam
Jong-Hee
JH
Kim
Young-Jin
YJ
Rhee
Joon-Haeng
JH
Yang
Deok-Hwan
DH
Kim
Yeo-Kyeoung
YK
Kim
Hyeoung-Joon
HJ
Chung
Ik-Joo
IJ
D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015847:Interleukin-4 / Q000378:metabolism; D020014:K562 Cells; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000628:therapy*; D010641:Phenotype; D053668:Syndecan-1 / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D018950:Lipopolysaccharide Receptors; D053668:Syndecan-1; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor