Selective targeting of tumoral vasculature: Comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin
Selective targeting of tumoral vasculature: Comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin
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DOI：
10.1002/ijc.10662
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发表时间：
2002-11-01
影响因子：
6.4
通讯作者：
Zardi, L
中科院分区：
文献类型：
--
作者：
Borsi, L;Balza, E;Zardi, L
我们最近证明，人重组单链抗体，L19，与纤维连接蛋白的ED-B结构域反应，血管生成的标志物，选择性靶向体内肿瘤血管。使用L19的可变区，我们构建并表达了人“小免疫蛋白”（SIP）和完整的人IgG 1，并在荷瘤小鼠中进行了生物分布研究，以比较3种L19形式[二聚体scFv（scFV）（2）、SIP和IgG 1]的血液清除率、体内稳定性和肿瘤靶向性能。所研究的肿瘤中不同抗体形式的积累是分子的清除率和体内稳定性的结果。使用SIP，肿瘤中的%ID/g比（scFV）2高2-5倍，在注射后4-6小时达到最大值。相比之下，在实验过程中，肿瘤中1gG 1的积累不断上升。然而，由于其缓慢的清除，144小时后%ID/g的肿瘤-血液比率仅为约3，相比之下，相同时间段后（scFV）2的比率为10，SIP的比率为70。根据临床需求和疾病，这3种完全人L19形式的不同体内行为可用于不同的诊断和/或治疗目的。此外，ED-B在人和小鼠中100%同源的事实确保了L19与人和鼠抗原的反应同样良好，这应该加速这些试剂向临床试验的转移。(C)2002 Wiley-Liss，Inc.
We recently demonstrated that a human recombinant scFv, L19, reacting with the ED-B domain of fibronectin, a marker of angiogenesis, selectively targets tumoral vasculature in vivo. Using the variable regions of L19, we constructed and expressed a human "small immunoprotein" (SIP) and a complete human 1gG1 and performed biodistribution studies in tumor-bearing mice to compare the blood clearance rate, in vivo stability and performance in tumor targeting of the 3 L19 formats [dimeric scFv (scFV)(2), SIP and 1gG1]. The accumulation of the different antibody formats in the tumors studied was a consequence of the clearance rate and in vivo stability of the molecules. Using the SIP, the %ID/g in tumors was 2-5 times higher than that of the (scFV)2, reaching a maximum 4-6 hr after injection. By contrast, the accumulation of 1gG1 in tumors constantly rose during the experiments. However, due to its slow clearance, the tumor-blood ratio of the %ID/g after 144 hr was only about 3 compared to a ratio of 10 for the (scFV)2 and 70 for the SIP after the same period of time. The different in vivo behavior of these 3 completely human L19 formats could be exploited for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. Furthermore, the fact that ED-B is 100% homologous in human and mouse, which ensures that L19 reacts equally well with the human and the murine antigen, should expedite the transfer of these reagents to clinical trials. (C) 2002 Wiley-Liss, Inc.