Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative mature dendritic cells enhances antitumor immunity
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- 作者：Liu ; Yongqing ; Zhang ; Weidong ; Chan ; Tim ; Saxena ; Anurag ; Xiang ; Jim
- 关键词：APC ; antigen presenting cell ; BM ; bone marrow ; cpm ; counts per minute ; CTL ; cytotoxic T lymphocyte ; DC ; dendritic cell ; DMEM ; Dulbecco’ ; s modified medium ; FCS ; fetal calf serum ; FITC ; fluorescein isothiocyanate ; GM-CSF ; granulocyte macrophage colony-s
- 刊名：Leukemia Research
- 出版年：2002
- 出版时间：August, 2002
- 年：2002
- 卷：26
- 期：8
- 页码：757-763
- 全文大小：129 K
文摘
Dendritic cell (DC)-tumor fusion hybrid vaccine which facilitates antigen presentation represents a new powerful strategy in cancer therapy. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between wild-type J558 or engineered J558-IL-4 myeloma cells secreting cytokine interleukin-4 (IL-4) and immature DCs (DC<sub>IMATsub>) or relative mature DCs (DC<sub>RMATsub>). DC<sub>RMATsub> displayed an up-regulated expression of immune molecules (Iad, CD40, CD54, CD80 and CD86) and certain cytokines/chemokines, and enhanced ability of allogeneic T cell stimulation when compared to DC<sub>IMATsub>. These DCs were fused with myeloma cells by polyethylene glycol (PEG). The fusion efficiency was approximately 20 % . Our data showed that immunization of C57BL/6 mice with DC<sub>RMATsub>/J558 hybrids induced protective immunity against a high dose of J558 tumor challenge (1×106 cells) in 3 out of 10 immunized mice, compared with no protection seen in mice immunized with DC<sub>IMATsub>/J558 hybrids. Furthermore, immunization of mice with engineered DC<sub>RMATsub>/J558-IL-4 hybrids elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro and induced more efficient protective immunity (10/10 mice; tumor free) against J558 tumor challenge in vivo than DC<sub>RMATsub>/J558 hybrid vaccines. The results demonstrate the importance of DC maturation in DC-tumor hybrid vaccines and indicate that the engineered fusion hybrid vaccines which combine gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.