A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts
A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts
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DOI：
10.1182/blood.v98.8.2535
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发表时间：
2001-10-15
期刊：
影响因子：
20.3
通讯作者：
Axworthy, D
中科院分区：
文献类型：
--
作者：
Press, OW;Corcoran, M;Axworthy, D
抗cd20单克隆抗体放射免疫治疗是一种治疗复发性b细胞淋巴瘤的新方法。然而，大多数接受常规放射性标记抗cd20抗体治疗的患者最终会复发，因为低的肿瘤与血液和肿瘤与正常器官的吸收放射性比限制了在没有造血干细胞支持的情况下可以安全给药的剂量。本研究评估了链亲和素-生物素“预靶向”方法改善拉莫斯淋巴瘤移植小鼠体内放射性生物分布的能力。注射预靶向链霉亲和素偶联抗cd20 1F5抗体，24小时后注射含生物素化n-乙酰半乳糖胺的“清除剂”，3小时后注射in- 11标记的dota生物素。与传统的In-111-1F5相比，预先靶向的肿瘤与血液的比率为3:1或更高，而传统的In-111-1F5为0.5:1或更低。肿瘤与正常器官的吸收放射性比在预先靶向治疗中高达56:1，但在常规的In-111-1F5治疗中为6:1或更低。治疗实验表明，需要400 μ Ci （14.8 MBq）或更多的常规Y-90-1F5才能获得主要的肿瘤反应，但该剂量在100%的小鼠中与致死毒性相关。与此形成鲜明对比的是，在800亩Ci (29.6 MBq) y -90- dota生物素的预靶向剂量下，小鼠的治愈率为89%，且毒性较小。这些数据表明，抗cd20预靶向治疗对改善目前b细胞淋巴瘤的治疗方案大有希望，值得进一步的临床前和临床试验。（Blood; 2001;98:2535-2543） (C) 2001由美国血液学会出版。
Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to-normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin "pretargeting" approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine-containing "clearing agent" and finally 3 hours later by In-11-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional In-111-1F5. Tumor-to-normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional In-111-1F5. Therapy experiments demonstrated that 400 mu Ci (14.8 MBq) or more of conventional Y-90-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 mu Ci (29.6 MBq) Y-90-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing. (Blood:2001;98:2535-2543) (C) 2001 by The American Society of Hematology.