Dantas-Barbosa Carmela, De Macedo Brigido Marcelo, Maranhao Andrea Queiroz
Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Cheney D, 28 Rue Laënnec, 69373 Lyon Cedex 08, France.
Laboratório de Biologia Molecular, CEL/IB, Universidade de Brasília, Campus Darcy Ribeiro, 70910-900, Brasília-DF, Brazil.
Int J Mol Sci. 2012;13(5):5420-5440. doi: 10.3390/ijms13055420. Epub 2012 May 4.
Since the advent of phage display technology, dating back to 1985, antibody libraries displayed on filamentous phage surfaces have been used to identify specific binders for many different purposes, including the recognition of tumors. Phage display represents a high-throughput technique for screening billions of random fusion antibodies against virtually any target on the surface or inside cancer cells, or even soluble markers found in patient serum. Many phage display derived binders targeting important tumor markers have been identified. Selection directed to tumoral cells' surfaces lead to the identification of unknown tumoral markers. Also the improvement of methods that require smaller amounts of cells has opened the possibility to use this approach on patient samples. Robust techniques combining an antibody library displayed on the phage surface and protein microarray allowed the identification of auto antibodies recognized by patient sera. Many Ab molecules directly or indirectly targeting angiogenesis have been identified, and one of them, ramucirumab, has been tested in 27 phase I-III clinical trials in a broad array of cancers. Examples of such antibodies will be discussed here with emphasis on those used as probes for molecular imaging and other clinical trials.
自1985年噬菌体展示技术问世以来,展示在丝状噬菌体表面的抗体库已被用于识别许多不同用途的特异性结合物,包括肿瘤识别。噬菌体展示是一种高通量技术,可针对癌细胞表面或内部的几乎任何靶点,甚至患者血清中发现的可溶性标志物,筛选数十亿种随机融合抗体。已经鉴定出许多针对重要肿瘤标志物的噬菌体展示衍生结合物。针对肿瘤细胞表面的筛选导致了未知肿瘤标志物的鉴定。此外,需要较少量细胞的方法的改进为在患者样本上使用这种方法开辟了可能性。将噬菌体表面展示的抗体库与蛋白质微阵列相结合的强大技术,使得能够鉴定出患者血清识别的自身抗体。已经鉴定出许多直接或间接靶向血管生成的抗体分子,其中一种,雷莫西尤单抗,已经在27项针对多种癌症的I-III期临床试验中进行了测试。这里将讨论此类抗体的例子,重点是用作分子成像探针和其他临床试验的抗体。