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Selective therapy of malignant lymphoma with novel radiolabeled antibody

新型放射性标记抗体选择性治疗恶性淋巴瘤

基本信息

批准号：
10670825
负责人：
ORIUCHI Noboru
金额：
$ 1.02万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In order to perform the radioimmunotherapy of malignant lymphoma with ィイD1131ィエD1I-labeled monoclonal antibody (ィイD1131ィエD1I-Ab) biodistribution and therapeutic effect of ィイD1131ィエD1I-Ab were evaluated in severely combined immunodeficiency mice (SCID mice) bearing human B-cell lymphoma. ィイD1131ィエD1I or ィイD1125ィエD1I was labeled in a sterile manner with anti-CD20 antibody which is highly specific for B-cell lymphoma. CD20-positive B-cell line RPMI 1788 was implanted in SCID mice and malignant lymphoma model was established. When tumors had grown to 7-10mm in diameter, ィイD1125ィエD1I-Ab was intravenously injected to quantitate the biodistribution and tumor accumulation. ィイD1125ィエD1I-Ab was accumulated in the tumor and tumor-to-normal ratio of uptake at 1, 2 and 7 days was 0.9, 1.5 and 3.4 respectively. Immunoscintigraphy with ィイD1131ィエD1I-Ab demonstrated tumor uptake.For radioimmunotherapy, groups of five mice with tumor were administered with Ab alone, ィイD1131ィエD1I-Ab, or doxorubicin.Antitumor effect of 100 μ Ci ィイD1131ィエD1I-Ab was equivalent to 67 μ g doxorubicin. Unclabeled Ab alone had some antitumor effect. Simultaneous administration of ィイD1131ィエD1I-Ab and doxorubicin augmented the efficacy without increasing therapeutic death. These results indicated that radioimmunotherapy with ィイD1131ィエD1I-labeled anti-CD20 Ab was effective on malignant lymphoma and doxorubicin could be jointly administered to augment the effect.

为探讨放射免疫治疗恶性淋巴瘤的可行性，采用人B细胞淋巴瘤严重联合免疫缺陷小鼠（SCID）模型，研究了放射免疫治疗恶性淋巴瘤的生物学分布和疗效。以无菌方式用对B细胞淋巴瘤具有高度特异性的抗CD 20抗体标记人CD 1131人CD 1 I或人CD 1125人CD 1 I。将CD 20阳性B细胞系RPMI 1788移植于SCID小鼠体内，建立恶性淋巴瘤模型。当肿瘤生长至直径7- 10 mm时，静脉注射顺铂D1125单克隆抗体D1 I-Ab以定量生物分布和肿瘤蓄积。结果表明，D1125单克隆抗体在肿瘤内有一定的蓄积，第1、2、7天的肿瘤/正常摄取比值分别为0.9、1.5、3.4。使用イD1131 D1 I-Ab的免疫闪烁显示肿瘤吸收。对于放射免疫治疗，对五只荷瘤小鼠进行单独Ab、イD1131 D1 I-Ab或多柔比星给药。100 μ CiイD1131 D1 I-Ab的抗肿瘤作用相当于67 μ g多柔比星。单独的未标记抗体具有一定的抗肿瘤作用。同时给予阿霉素D1131和阿霉素D1 I-Ab可增强疗效，而不会增加治疗性死亡。结果表明，用阿霉素D1131标记的抗CD 20抗体放射免疫治疗恶性淋巴瘤是有效的，阿霉素可以联合使用以增强效果。