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分泌粒细胞-巨噬细胞集落刺激因子的冻干骨髓瘤细胞诱导抗肿瘤免疫

Induction of anti-tumor immunity by lyophilized myeloma cells secreting GM-CSF.

作者信息

Wu Sheng, Yuan Dawen, Liu Jian-Ning, Tan Xiang-Yang

机构信息

Institute of Molecular Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, P.R. China.

出版信息

Oncol Rep. 2007 Jan;17(1):129-33.

Abstract

We have previously demonstrated that a low dose of live myeloma FO cells induced a cellular immunity against tumor without additional modulating factors. In the present study, lyophilized myeloma FO cells were used to induce anti-tumor immunity. In a myeloma vaccination model, immunization with lyophilized myeloma FO cells alone induced a slight response. However, the immunity was dramatically enhanced by myeloma FO cells transfected with a recombinant adenovirus, Adv-1/GM-CSF. The immunocytochemical staining of Adv-1/GM-CSF transfected myeloma FO cells confirmed that more than 90% of cells were positive with GM-CSF expression. Results of sandwich ELISA showed the amount of secreted GM-CSF was 240 ng/24 h per 10(6) cells. Immunization with lyophilized myeloma FO cells secreting GM-CSF prevented the tumor growth in 60% of BALB/c mice. Antibodies against myeloma FO cells were found in the sera of immunized mice. Tumor-specific T-cell response was also evaluated using cytotoxic T lymphocyte assay. In conclusion, lyophilized myeloma FO cells secreting GM-CSF can be used as a potent vaccine to induce strong and protective anti-tumor immunity.

摘要

我们之前已经证明,低剂量的活骨髓瘤FO细胞在没有额外调节因子的情况下可诱导针对肿瘤的细胞免疫。在本研究中,使用冻干的骨髓瘤FO细胞来诱导抗肿瘤免疫。在骨髓瘤疫苗接种模型中,单独用冻干的骨髓瘤FO细胞免疫诱导了轻微的反应。然而,用重组腺病毒Adv-1/GM-CSF转染的骨髓瘤FO细胞可显著增强免疫。Adv-1/GM-CSF转染的骨髓瘤FO细胞的免疫细胞化学染色证实,超过90%的细胞GM-CSF表达呈阳性。夹心ELISA结果显示,每10(6)个细胞每24小时分泌的GM-CSF量为240 ng。用分泌GM-CSF的冻干骨髓瘤FO细胞免疫可使60%的BALB/c小鼠的肿瘤生长受到抑制。在免疫小鼠的血清中发现了抗骨髓瘤FO细胞的抗体。还使用细胞毒性T淋巴细胞试验评估了肿瘤特异性T细胞反应。总之,分泌GM-CSF的冻干骨髓瘤FO细胞可作为一种有效的疫苗来诱导强大的保护性抗肿瘤免疫。

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