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Radio immunotherapy of malignant tumors by pretargeting

恶性肿瘤的预靶向放射免疫治疗

基本信息

批准号：
11670911
负责人：
HOSONO Makoto
金额：
$ 2.05万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

项目摘要

The "affinity enhancement system", a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for the targeting of carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody.Antineural cell adhesion molecule/antihistamine bispecific anti-body NKI NBLIJ79 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NC1-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 1251-labeled bivalent histamine hapten. 1251-labeled in tact NKINBLI was injected into other groups of mice. Biodisributions were examined as a function of time.In mice of the two-step targeting, tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 ± 1.1, 10.8 ± 13.2 and 4.6 ± 4.7, respectively, at 5 h, whereas 1251-labeled NK1NBL1 showed tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 ± 0.1, 1.1 ± 0.2 and 0.9 ± 0.1, respectively, at 5 h. Dosimetry showed that tumor-to-liver and -to-bone marrow ratios of absorbed irradiation doses were 14.3 and 16.8 for the two-step method and 4.2 and 2.6 for the one-step method. This suggested that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1.This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer by giving enhanced tumor-to-normal tissue contrast.

“亲和增强系统”是一种使用双特异性抗体和放射性标记的二价半抗原的两步靶向技术，已被报道用于靶向表达癌胚抗原的肿瘤。本研究的目的是利用抗神经细胞粘附分子抗体评价该方法靶向人小细胞肺癌的疗效。通过将NK1NBL1的Fab'片段与抗组胺679的Fab片段偶联，制备了抗神经细胞粘附分子/抗组胺双特异性抗体NKI NBLIJ79。用表达神经细胞粘附分子的NC1-H69小细胞肺癌细胞接种胸腺小鼠，接种双特异性抗体，48 h后注射1251标记的二价组胺半抗原。将1251标记的NKINBLI注射到其他各组小鼠。生物分布作为时间的函数进行了检查。在老鼠身上的两步定位、tumor-to-blood tumor-to-liver tumor-to-kidney比率分别为1.4±1.1,10.8±13.2,4.6±4.7,分别在5 h,而1251 -标记NK1NBL1显示tumor-to-blood, tumor-to-liver和tumor-to-kidney比率为0.3±0.1,1.1±0.2,0.9±0.1,分别在5 h。剂量测定法显示tumor-to-liver和骨骼骨髓比率辐照吸收剂量分别为14.3和16.8的两步方法,4.2和2.6的一步到位的方法。提示亲和增强系统可增强抗神经细胞粘附分子抗体NK1NBL1的治疗潜力。这种两步靶向方法通过增强肿瘤与正常组织的对比，似乎有望用于小细胞肺癌的诊断和治疗。