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粒细胞-巨噬细胞集落刺激因子和粒细胞集落刺激因子增强抗GD2单克隆抗体220-51对人神经母细胞瘤的体内外抗肿瘤活性

Enhancement of in vitro and in vivo anti-tumor activity of anti-GD2 monoclonal antibody 220-51 against human neuroblastoma by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

作者信息

Fukuda M, Horibe K, Furukawa K

机构信息

Department of Pediatrics, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

出版信息

Int J Mol Med. 1998 Oct;2(4):471-5. doi: 10.3892/ijmm.2.4.471.

Abstract

We have evaluated the anti-tumor effect of anti-GD2 mouse monoclonal antibody (mAb) 220-51 against human neuroblastoma cell line TGW in vitro and in vivo. The mAb 220-51 was able to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) using human effector cells. In the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte ADCC was significantly augmented in vitro. When mAb 220-51 was administered to tumor-bearing nude mice, tumor growth was significantly inhibited as compared with untreated controls. Administration of recombinant murine GM-CSF in combination with mAb 220-51 significantly enhanced the anti-tumor effect of mAb in vivo. Recombinant human granulocyte colony-stimulating factor (G-CSF) combined with mAb 220-51 was also able to enhance it, although granulocyte ADCC was not affected by the presence of recombinant human G-CSF in vitro. Moreover, GM-CSF and G-CSF work additively to enhance the anti-tumor effect of mAb 220-51 in vivo. The GM-CSF and G-CSF may have a clinical potency in immunotherapy with anti-GD2 mAb for the treatment of neuroblastoma.

摘要

我们已经在体外和体内评估了抗GD2小鼠单克隆抗体(mAb)220-51对人神经母细胞瘤细胞系TGW的抗肿瘤作用。mAb 220-51能够利用人效应细胞介导补体依赖性细胞毒性(CDC)和抗体依赖性细胞毒性(ADCC)。在重组人粒细胞-巨噬细胞集落刺激因子(GM-CSF)存在的情况下,粒细胞ADCC在体外显著增强。当将mAb 220-51给予荷瘤裸鼠时,与未处理的对照组相比,肿瘤生长显著受到抑制。重组鼠GM-CSF与mAb 220-51联合给药显著增强了mAb在体内的抗肿瘤作用。重组人粒细胞集落刺激因子(G-CSF)与mAb 220-51联合使用也能够增强其作用,尽管粒细胞ADCC在体外不受重组人G-CSF存在的影响。此外,GM-CSF和G-CSF在体内协同作用以增强mAb 220-51的抗肿瘤作用。GM-CSF和G-CSF在抗GD2 mAb免疫治疗神经母细胞瘤中可能具有临床效力。

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