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KMID : 0366220060410030186
Korean Journal of Hematology
2006 Volume.41 No. 3 p.186 ~ p.193
Induction of Myeloma Cell Line-specific Cytotoxic T Lymphocytes using Monocyte-derived Dendritic Cells Pulsed with Myeloma Cell Line Lysates
Park Myong-Suk

Park Jung-Sun
Kang Hyun-Kyu
Kim Sang-Ki
Won Jong-Ho
Choi Bo-Hwa
Shin Shi-Won
Zhu Xiao-Wei
Jin Chun-Ji
Thanh-Nhan Nguyen Pham
Cho Duck
Nam Jong-Hee
Kim Young-Jin
Kim Yeo-Kyeoung
Yang Deok-Hwan
Chung Ik-Joo
Kim Hyeoung-Joon
Lee Je-Jung
Abstract
Background: In multiple myeloma (MM), the idiotype (ID) determinant of the paraprotein has been used for immunotherapy using dendritic cells (DCs). However, ID-specific immune responses showed limited clinical responses after the Id vaccination. Therefore, an alternative approach using DCs pulsed with other tumor antigens is required.

Methods: We investigated the possibility of immunotherapy for MM using myeloma cell line-specific cytotoxic T lymphocytes (CTLs), that were stimulated in vitro by monocyte-derived DCs pulsed with the myeloma cell line ysates. CD14+ cells isolated from the peripheral blood of HLA-A0201+ healthy donors were cultured in the presence of GM-CSF and IL-4. On day 6, the immature DCs were pulsed with the myeloma cell line lysates (IM-9: HLA0201+ and ARH-77: HLA0201+), and then maturation of DCs was induced by the addition of TNF-¥á for 2 days. CTL lines were generated by a 2 time stimulation with DCs to the autologous CD3+ T cells.

Results: DCs pulsed with myeloma cell lysates showed the production of IL-12p70, but less than that of unpulsed DCs. CTLs lines stimulated with the DCs pulsing, for the myeloma cell line lysates, showed potent cytotoxic activities against autologous target cells, but not against HLA-A2£­ cell lines (RPMI-8226). Mature DCs pulsed with the myeloma cell line lysates showed a higher stimulatory capacity for autologous CTL when compared with mature non-pulsed DCs.

Conclusion: These results suggest that DCs pulsed with the myeloma cell line lysates can generate potent myeloma cell line-specific CTLs for the myeloma cell-based immunotherapeutic approach in MM.
KEYWORD
Dendritic cells, Myeloma, Lysate, Cell line
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