Efficient tumor targeting by single-domain antibody fragments of camels
Efficient tumor targeting by single-domain antibody fragments of camels
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DOI：
10.1002/ijc.10212
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发表时间：
2002-03-20
影响因子：
6.4
通讯作者：
Revets, H
中科院分区：
文献类型：
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作者：
Cortez-Retamozo, V;Lauwereys, M;Revets, H
在骆驼中发现的缺乏轻链的功能性重链抗体（VHH）的可变结构域构成最小的完整抗原结合结构域片段。研究了两个骆驼单结构域片段cAb-Lys 2和cAb-Lys 3（分别识别溶菌酶的重叠表位，解离常数为2 nM和65 nM）和二价cAb-Lys 3靶向在其膜上表达溶菌酶的转基因肿瘤的能力。生物分布研究表明，这些非免疫原性单体和二价骆驼单结构域抗原结合剂特异性靶向表达溶菌酶的肿瘤和转移性病变。过量的抗体从血液循环中迅速消除，在正常器官中未观察到cAb滞留。2和8小时的肿瘤与器官cAb比分别在（2.1-10.8）：1和（6.2-23.7）：1范围内。肿瘤保留的程度和特异性与重组骆驼单结构域片段对其抗原的亲和力以及其单价单体（15 kDa）或二价形式（33 kDa）无关。本研究证明了骆驼单结构域片段的成功和特异性体内靶向肿瘤。由于它们的小尺寸、可溶性行为以及因为它们是非免疫原性的并且与对于常规抗体抗原性较低的表位相互作用，这可能为它们未来用作肿瘤靶向载体打开前景。(C)2002 Wiley-Liss，Inc.
The variable domain of functional heavy chain antibodies (VHH) devoid of light chains, found in camels, constitute the smallest intact antigen-binding domain fragment. Two camel single-domain fragments, cAb-Lys2 and cAb-Lys3, recognizing an overlapping epitope of lysozyme with a dissociation constant of 2 nM and 6S nM, respectively, and a bivalent cAb-Lys3 were investigated for their ability to target transgenic tumors expressing lysozyme on their membrane. Biodistribution studies revealed that these non-immunogenic monomeric and bivalent camel single-domain antigen binders specifically target lysozyme-expressing tumors and metastatic lesions. The excess of antibody is rapidly eliminated from the blood circulation and no cAb retention was observed in normal organs. The tumor to organ cAb-ratios at 2 and 8 hr were in the (2.1-10.8):1 and (6.2-23.7):1 range, respectively. The degree and specificity of tumor retention is independent of the affinity of the recombinant camel single-domain fragments for their antigen and from their univalent monomeric (15 kDa) or bivalent format (33 kDa). This study demonstrates the successful and specific in vivo targeting of tumors by camel single-domain fragments. It may open perspectives for their future use as tumor-targeting vehicle, due to their small size, soluble behaviour and because they are non-immunogenic and interact with epitopes that are less antigenic for conventional antibodies. (C) 2002 Wiley-Liss, Inc.