The advantage of residualizing radiolabels for targeting B‐cell lymphomas with a radiolabeled anti‐CD22 monoclonal antibody

The advantage of residualizing radiolabels for targeting B‐cell lymphomas with a radiolabeled anti‐CD22 monoclonal antibody
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使用放射性标记的抗 CD22 单克隆抗体靶向 B 细胞淋巴瘤时残留放射性标记的优势

DOI:
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发表时间:
1997
影响因子:
6.4
通讯作者:
D. Goldenberg
D. Goldenberg
中科院分区:
医学1区
文献类型:
--
作者:
M. Mattes;L. Shih;S. Govindan;R. Sharkey;G. L. Ong;H. Xuan;D. Goldenberg

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已知与B细胞淋巴瘤结合的CD22抗体(Abs)被内化并迅速分解代谢。因此,可以预期的是,CD22作为放射免疫治疗靶标的使用应该通过使用“残化”放射性标记来加强,这些放射性标记在与它们结合的Ab分解代谢后被捕获在细胞内。我们的研究旨在用Ab LL2来评估这一假设。在最初的实验中,我们发现LL2的结合强烈依赖于温度,在37°C时的结合比在0°C时的结合高约15倍。一系列实验表明,这种差异是由于抗原在低温下发生构象变化,使LL2表位部分被阻断。在体外,残留标记——包括125I‐双乙酰氨基醇和111In‐dtpa——在细胞中保留的时间比传统的碘标记长得多。在体内,残留标记在裸鼠Ramos B细胞淋巴瘤异种移植物的摄取方面也显示出明显的优势。然而,与许多癌症异种移植相比,异种移植的绝对Ab摄取非常低,这似乎部分是由于B细胞淋巴瘤异种移植的血管特性。Int。[j] .中国生物医学工程学报,2009。©1997 Wiley‐Liss Inc。
CD22 antibodies (Abs) bound to B‐cell lymphomas are known to be internalized and catabolized rapidly. Therefore, it would be expected that use of CD22 as a target for radioimmunotherapy should be enhanced by the use of “residualizing” radiolabels, which are trapped within the cell after catabolism of the Ab to which they had been conjugated. Our study was intended to evaluate this hypothesis using Ab LL2. In initial experiments, we found that LL2 binding was strongly temperature dependent, with approximately 15‐fold greater binding at 37°C than at 0°C. A series of experiments suggested that this difference is due to a conformational change in the antigen at low temperature, so that the LL2 epitope is partially blocked. In vitro, residualizing labels—including 125I‐dilactitol tyramine and 111In‐DTPA—were retained by cells much longer than a conventional iodine label. In vivo, residualizing labels also showed a marked advantage in terms of uptake by Ramos B‐cell lymphoma xenografts in nude mice. However, the absolute Ab uptake by xenografts was quite low, in comparison with results obtained with many carcinoma xenografts, which appears to be due in part to vascular properties of the B‐cell lymphoma xenografts. Int. J. Cancer 71:429‐435, 1997. © 1997 Wiley‐Liss Inc.
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