Tools for active specific immunotherapy with anti-idiotype antibodies in human renal cell carcinoma

使用抗独特型抗体对人肾细胞癌进行主动特异性免疫治疗的工具

• 批准号: 07671748
• 负责人: UEMURA Hirotsugu
• 金额: $ 1.47万
• 依托单位: NARA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671748/
• 关键词: Renal cell carcinoma; MAbG250; Anti-idiotype antibody; Immunotherapy; 免疫療法

In apite of the increasing success in the management of urological malignancies, curative treatment of renal cell carcinoma (RCC) patients with metastatic disease still remains extremely difficult. Even with the multitude of therapeutic strategies, almost no improvement of the survival for these patients has been established in the last decade. It is well known that RCC is relatively resistant to conventional therapies and immunotherapy seems to be the most promising treatment for disseminated RCC.Obviously, the development of new therapeutic approach is necessary. We have developed internal image anti-idhiotype antibodies (Ab2) raised against MAbG250 which recognizes a large proportion of RCC,and also have shown that Ab2 vaccination resulted in the destruction of established tumor in mice. In the present study, we investigate therapeutic effects of MAbG250 immunotherapy in combination with cytokines (exp.1) and internal image Ab2 induced antisera (Ab3-82)(exp.2) in mice with RCC xenog … More rafts. Method : exp.1) Nu-nu BALB/c mice with approximately 20mm NUR2 human RCC xenografts were divided into 10 groups, i.e., gr.1 : control.gr.2 : IL-2, gr.3 : rm-IFN,gr.4 : MCSF,gr.5 : MAbG250, gr.6 : IL-2/MAbG250, gr. 7 : rm-IFN/MAbG250, gr.8 : MCSF/MAbG250, gr.9 : IL-2/IFN,gr.10 : IL-2/rm-IFN/MAbG250. Mice were treated with peri-tumor injection of 200 U/g mouse cytokines 5 days a week for 6 weeks. exp.2) Nu/nu mice with NUR2 xenografts were divided into 4 groups and treated with the following schedule for 6 weeks ; gr.1 : NMS (control)(0.2ml, i.p.3/week), gr.2 : MAbG250/IL-2/rm-IFN,gr.3 : Ab3-82 (0.2ml, i.p.3/week), gr.4 : Ab3-82+MCSF.Results : (exp.1) Treatment of NUR2 with IFN,IL-2, MAbG250, MCSF or IL-2/MAbG250 resulted in significant tumor growth inhibition (p<0.05) as compared to control group. In the remaining 3 groups, i.e., IL-2/IFN,IFN/MAbG250, IL-2/IFN/MAbG250, the tumor growth inhibition was greater than in the previous groups. (exp.2) Treatment of NUR2 RCC xenografts with IL-2/IFN/MAbG250, Ab3 based immunotherapy resulted in significant tumor growth inhibition compared to control group (gr.2,3 : p<0.01, gr.4 : p<0.0001). These findings suggest that Ab2 vaccination might be useful for specific immunotherapy in RCC patients. Less

随着泌尿系统恶性肿瘤治疗的日益成功，肾细胞癌（RCC）转移性疾病的根治性治疗仍然非常困难。即使有多种治疗策略，在过去的十年中，这些患者的生存率几乎没有改善。众所周知，肾癌对常规治疗具有较强的抵抗力，免疫治疗是目前治疗肾癌的最有希望的方法，因此，寻找新的治疗方法是非常必要的。我们已经开发了针对MAbG 250产生的内部图像抗独特型抗体（Ab 2），其识别大比例的RCC，并且还显示Ab 2疫苗接种导致小鼠中已建立的肿瘤的破坏。在本研究中，我们研究了MAbG 250免疫治疗与细胞因子（实验1）和内部图像Ab 2诱导的抗血清（Ab 3 -82）（实验2）联合治疗RCC异种小鼠的疗效。 ...更多信息 木筏方法：实验1）将具有约20 mm厚的人RCC异种移植物的Nu-nu BALB/c小鼠分为10组，即，组1：control.gr.2：IL-2，3级：rm-IFN，4级：MCSF，等级5：组6：IL-2/MAbG 250，组7：rm-IFN/MAbG 250，组8：MCSF/MAbG 250，组9：IL-2/IFN，组10：IL-2/rm-IFN/MAbG 250。用肿瘤周围注射200 U/g小鼠细胞因子治疗小鼠，每周5天，持续6周。实验2）将具有Nm 2异种移植物的Nu/nu小鼠分成4组，并用以下方案治疗6周;组1：NMS（对照）（0.2 ml，i.p.3/周），第2组：MAbG 250/IL-2/rm-IFN，第3组：Ab 3 -82结果：（实验1）IFN、IL-2、MAbG 250、MCSF或IL-2/MAbG 250处理组与对照组相比，肿瘤生长明显受到抑制（p<0.05）。在其余3组中，即，IL-2/IFN、IFN/MAbG 250、IL-2/IFN/MAbG 250对肿瘤生长的抑制作用均大于前几组。（实验2）与对照组相比，用基于IL-2/IFN/MAbG 250、Ab 3的免疫疗法处理102 RCC异种移植物导致显著的肿瘤生长抑制（组2、3：p<0.01，组4：p<0.0001）。这些结果表明，Ab 2疫苗接种可能是有用的RCC患者的特异性免疫治疗。少

项目成果

Uemura, H.and Okajima, E.: "Anti-idiotype antibody bearing the internal image of tumor-associated antigen" Clin.Immunol.Jan.28. 134-138 (1996)

Uemura, H. 和 Okajima, E.：“带有肿瘤相关抗原内部图像的抗独特型抗体”Clin.Immunol.Jan.28。

Uemura,H.: "Induction of tumor regression by passive transfer of antibody from mice vaccinated with anti-idiotype antibodies resembling a human renal cell carcinoma-associated antigen" Urol.Oncol.1. 73-79 (1995)

Uemura,H.：“通过从接种了类似于人肾细胞癌相关抗原的抗独特型抗体的小鼠中被动转移抗体来诱导肿瘤消退”Urol.Oncol.1。

植村天受: "腎癌におけるActive specific immunotherapy-抗イディオタイプ抗体の有用性について-" Biotherapy. 9. 294-295 (1995)

Tenke Uemura：“肾癌的主动特异性免疫疗法 - 抗独特型抗体的用途 -” 生物疗法 9. 294-295 (1995)。

植村天受: "腎細胞癌における抗体および抗イディオタイプ抗体による治療効果" Biotherapy. 11(in press). (1997)

Tenke Uemura：“肾细胞癌中抗体和抗独特型抗体的治疗效果”生物疗法 11（出版中）。

Uemura, H.: "Potential tools for anti-idiotype antibodies for active specific immunotherapy in human renal cell carcinoma" J.Nara Med.Ass.47. 76-87 (1996)

Uemura, H.：“用于人肾细胞癌主动特异性免疫治疗的抗独特型抗体的潜在工具”J.Nara Med.Ass.47。