化学编程靶向豆荚蛋白酶和αvβ3整合素的双特异性抗体介导强大的抗肿瘤作用。
Chemically Programmed Bispecific Antibody Targeting Legumain Protease and αvβ3 Integrin Mediates Strong Antitumor Effects.
作者信息
Liu Yuan, Goswami Rajib K, Liu Cheng, Sinha Subhash C
机构信息
†Departments of Immunology and Microbial Sciences and §Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
出版信息
Mol Pharm. 2015 Jul 6;12(7):2544-50. doi: 10.1021/acs.molpharmaceut.5b00257. Epub 2015 Jun 9.
A chemically programmed bispecific antibody (cp-bsAb) that targeted cysteine protease legumain and αvβ3 integrin has been prepared using the aldolase antibody chemical programming (AACP) strategy. In vitro evaluation of the anti-legumain, anti-integrin cp-bsAb and its comparison with cpAbs targeting either integrin or legumain have shown that the former possesses superior functions, including receptor binding and inhibitory effects on cell proliferation as well as capillary tube formation, among all three cpAbs. The anti-legumain, anti-integrin cp-bsAb also inhibited growth of primary tumor more effectively than either anti-legumain or anti-integrin cpAb as observed in the MDA-MB-231 human breast cancer mouse model. The AACP-based cp-bsAb, which contains a generic aldolase antibody, can also serve as a suitable platform for combination therapy, where two equally potent compounds are used to target extracellular receptors.
利用醛缩酶抗体化学编程（AACP）策略制备了一种靶向半胱氨酸蛋白酶legumain和αvβ3整合素的化学编程双特异性抗体（cp-bsAb）。对该抗legumain、抗整合素cp-bsAb进行体外评估，并将其与靶向整合素或legumain的cpAbs进行比较，结果表明，在所有三种cpAbs中，前者具有更优异的功能，包括受体结合、对细胞增殖以及毛细管形成的抑制作用。在MDA-MB-231人乳腺癌小鼠模型中观察到，抗legumain、抗整合素cp-bsAb比抗legumain或抗整合素cpAb更有效地抑制原发性肿瘤生长。基于AACP的cp-bsAb包含一种通用的醛缩酶抗体，它也可以作为联合治疗的合适平台，即使用两种同样有效的化合物靶向细胞外受体。
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