KMID : 0939920110430010056
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´ëÇѾÏÇÐȸÁö 2011 Volume.43 No. 1 p.56 ~ p.66
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Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer
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Park Min-Ho
Yang Deok-Hwan Kim Mi-Hyun Jang Jae-Hong Jang Yoon-Young Lee Youn-Kyung Jin Chun-Ji Pham Than Nhan Nguyen Thi Truc Anh Nguyen Lim Mi-Seon Lee Hyun-Ju Hong Cheol-Yi Yoon Jung-Han Lee Je-Jung
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Abstract
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Purpose: Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (¥á DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
Materials and Methods: ¥áDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed ¥áDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
Results: The ¥áDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the ¥áDC1s were loaded with tumor antigens. The ¥áDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by ¥áDC1s loaded with apoptotic MCF-7 cells.
Conclusion: Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.
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KEYWORD
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Dendritic cells, Breast neoplasms, Allogeneic, Cytotoxic T lymphocytes, Immunotherapy
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