Original Article

Korean J Hematol 2006; 41(3):

Published online September 30, 2006

https://doi.org/10.5045/kjh.2006.41.3.186

© The Korean Society of Hematology

다발성골수종 세포주로 부가된 단구-유래 수지상세포를 이용한 골수종 세포주-특이 세포독성 T 림프구의 유도

박명숙, 박정선, 강현규, 김상기, 원종호, 최보화, 신시원, 주효미, 김춘희, 니엔판탄냔, 조덕, 남종희, 김영진, 김여경, 양덕환, 정익주, 김형준, 이제중

화순전남대학교병원 암백신팀, 전남대학교 의과대학 혈액종양내과, 순천향대학교 의과대학 혈액종양내과, 공주대학교 산업과학대학 특수동물학과

Induction of Myeloma Cell Line-specific Cytotoxic T Lymphocytes using Monocyte-derived Dendritic Cells Pulsed with Myeloma Cell Line Lysates

Myong Suk Park, Jung Sun Park, Hyun Kyu Kang, Sang Ki Kim, Jong Ho Won, Bo Hwa Choi, Shi Won Shin, Xiao Wei Zhu, Chun Ji Jin, Thanh Nhan Nguyen Pham, Duck Cho, Jong Hee Nam, Young Jin Kim, Yeo Kyeoung Kim, Deok Hwan Yang, Ik Joo Chung, Hyeoung Joon Kim, Je Jung Lee

Cancer Vaccine Team, Chonnam National University Hwasun Hospital, Jeonnam,
Department of Hematology, Oncology, Chonnam National University Medical School, Gwangju, Soon Chun Hyang University College of Medicine, Seoul,
Department of Companion Laboratory Animal, Science College of Industrial Science, Kongju National University, Gongju, Korea

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-Ձ 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.

Keywords Dendritic cells, Myeloma, Lysate, Cell line

Article

Original Article

Korean J Hematol 2006; 41(3): 186-193

Published online September 30, 2006 https://doi.org/10.5045/kjh.2006.41.3.186

Copyright © The Korean Society of Hematology.

다발성골수종 세포주로 부가된 단구-유래 수지상세포를 이용한 골수종 세포주-특이 세포독성 T 림프구의 유도

박명숙, 박정선, 강현규, 김상기, 원종호, 최보화, 신시원, 주효미, 김춘희, 니엔판탄냔, 조덕, 남종희, 김영진, 김여경, 양덕환, 정익주, 김형준, 이제중

화순전남대학교병원 암백신팀, 전남대학교 의과대학 혈액종양내과, 순천향대학교 의과대학 혈액종양내과, 공주대학교 산업과학대학 특수동물학과

Induction of Myeloma Cell Line-specific Cytotoxic T Lymphocytes using Monocyte-derived Dendritic Cells Pulsed with Myeloma Cell Line Lysates

Myong Suk Park, Jung Sun Park, Hyun Kyu Kang, Sang Ki Kim, Jong Ho Won, Bo Hwa Choi, Shi Won Shin, Xiao Wei Zhu, Chun Ji Jin, Thanh Nhan Nguyen Pham, Duck Cho, Jong Hee Nam, Young Jin Kim, Yeo Kyeoung Kim, Deok Hwan Yang, Ik Joo Chung, Hyeoung Joon Kim, Je Jung Lee

Cancer Vaccine Team, Chonnam National University Hwasun Hospital, Jeonnam,
Department of Hematology, Oncology, Chonnam National University Medical School, Gwangju, Soon Chun Hyang University College of Medicine, Seoul,
Department of Companion Laboratory Animal, Science College of Industrial Science, Kongju National University, Gongju, Korea

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-Ձ 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.

Keywords: Dendritic cells, Myeloma, Lysate, Cell line

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