Basic study for clinical application of anti-ganglioside D2 monoclonal antibody against neuroblastoma

抗神经节苷脂D2单克隆抗体抗神经母细胞瘤临床应用基础研究

• 批准号: 05670668
• 负责人: HORIBE Keizo
• 金额: $ 1.47万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670668/
• 关键词: Neuroblastoma; Anti-ganglioside D2 antibody; Immunotherapy; Cytokine; 抗ガングリオシドD_2モノクローナル抗体; 抗ガングリオシドD2モノクローナル抗体

In order to apply anti-ganglioside D2 (GD2) mouse monoclonal antibodies (moAb) as a specific therapy for neuroblastoma, 3 kinds of anti-GD2 moAb were studied about the tissue specificity, anti-tumor effect in vitro and in vivo, and its augmentation with hematopoietic cytokines.1.MoAbs 220-51, A1.410 and 3F8 specifically responded to human neuroblastoma cell lines and tumor samples, and responded only to brain tissue among normal tissues tested.2.Imaging study with injection of radiolabelled 220-51 revealed its specific consentration to the tumor region in the nude mouse transplanted with neuroblastoma cell lines.3.All of 220-51, A1.410 and 3F8 were demonstrated the complement dependent cytotoxicity and antibody dependent cellular cytotoxicity against neuroblastoma cell lines.4.Antibody dependent cellular cytotoxicity by neutorophils was enhanced by reconbinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF).5.MoAb 220-51 had the inhibition activity against tumor progression by itself. The actvity was inhibited more strongly by the antibody combined with recombinant mouse GM-CSF (rmGM-CSF) or recombinant human granulocyte-CSF (rhG-CSF), and it was inhibited most strongly by the antibody combined with both rmGM-CSF and rhG-CSF.These findings suggested that anti-GD2 moAb must be useful for the clinical application in neuroblastoma therapy.

In order to apply anti-ganglioside D2 (GD2) mouse monoclonal antibodies (moAb) as a specific therapy for neuroblastoma, 3 kinds of anti-GD2 moAb were studied about the tissue specificity, anti-tumor effect in vitro and in vivo, and its augmentation with hematopoietic cytokines.1.MoAbs 220-51, A1.410 and 3F8特别对人类神经细胞瘤细胞系和肿瘤样品做出了反应，并且仅对正常组织中的脑组织作出反应。细胞毒性和抗体依赖性细胞细胞毒性对神经母细胞瘤细胞系的细胞毒性。4。通过重新结合人类粒细胞巨噬细胞 - 巨噬细胞刺激因子（RHGM-CSF）（RHGM-CSF）的抗体依赖性细胞细胞毒性通过中性粒细胞增强了。抗体与重组小鼠GM-CSF（RMGM-CSF）或重组人类粒细胞-CSF（RHG-CSF）相结合，更强烈地抑制了该作用，并且它被抗体最强烈抑制了抗体，抗体与RMGM-CSF和RHG-CSF的临床均具有适用于RMGM-CSF和RHG-CSF的应用。神经母细胞瘤治疗。