Comparison of fusion phage libraries displaying V-H or single-chain Fv antibody fragments derived from the antibody repertoire of a vaccinated melanoma patient as a source of melanoma-specific targeting molecules
Comparison of fusion phage libraries displaying V-H or single-chain Fv antibody fragments derived from the antibody repertoire of a vaccinated melanoma patient as a source of melanoma-specific targeting molecules
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DOI：
10.1073/pnas.94.17.9261
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发表时间：
1997-08-19
影响因子：
11.1
通讯作者：
Garen, A
中科院分区：
文献类型：
--
作者：
Cai, XH;Garen, A
V-H和V-L随机组合的单链抗体融合噬菌体库先前使用接种疫苗的黑素瘤患者的抗体库中的可变重链和轻链（可变重链和轻链）结构域来分离特异性结合黑素瘤细胞的克隆。意外的发现是克隆之一编码大部分V-L结构域缺失的截短的scFv分子，表明单独的V-H结构域可以表现出肿瘤特异性结合。在该报道中，将含有与V-L结构域不相关的V-H结构域的V-H融合噬菌体文库与作为黑素瘤特异性克隆来源的scFv融合噬菌体文库进行比较;两个文库都含有来自接种的黑素瘤患者的相同V-H结构域。结果证明克隆可以从两个文库中分离，并且两个文库都应该用于优化分离与不同表位结合的克隆的机会。虽然这种策略只针对黑色素瘤进行了测试，但它也适用于其他癌症。由于它们的小尺寸、人源性和对细胞表面肿瘤抗原的特异性，V-H和scFv分子作为用于诊断和治疗程序的肿瘤靶向分子具有显著的优势，并且还可以用作用于鉴定同源肿瘤抗原的探针。
A single-chain Fv (scFv) fusion phage library derived from random combinations of V-H and V-L (variable heavy and light chains) domains in the antibody repertoire of a vaccinated melanoma patient was previously used to isolate clones that bind specifically to melanoma cells, An unexpected finding was that one of the clones encoded a truncated scFv molecule with most of the V-L domain deleted, indicating that a V-H domain alone can exhibit tumor-specific binding, In this report a V-H fusion phage library containing V-H domains unassociated with V-L domains was compared with a scFv fusion phage library as a source of melanoma-specific clones; both libraries contained the same V-H domains from the vaccinated melanoma patient, The results demonstrate that the clones can be isolated from both libraries, and that both libraries should be used to optimize the chance of isolating clones binding to different epitopes. Although this strategy has been tested only for melanoma, it is also applicable to other cancers. Because of their small size, human origin and specificity for cell surface tumor antigens, the V-H and scFv molecules have significant advantages as tumor-targeting molecules for diagnostic and therapeutic procedures and can also serve as probes for identifying the cognate tumor antigens.