抗体—药物共轭连结技术(ADC)是一种将基因工程单株抗体与杀癌细胞药物结合在一起的技术。在7月出版的《自然—生物技术》期刊上，研究人员报告一种具有癌症治疗潜力的新型ADC技术，这种方法有望减少药物对健康细胞的伤害，副作用也更小。
在敏锐识别癌细胞的同时，以肿瘤为靶标的抗体也能忽略正常细胞，抗体的这种特征被用于靶向药物输送的研发中，研究人员希望将化学治疗药物缚束到这种抗体上，形成ADC药物。以前制造ADC药物的方法具有多种混合效果，部分抗体会比其他抗体携带更多的药物，因此很难确定最佳的药物用量。
如今，美国Genentech公司William Mallet和同事研制出一种可确定携带药物量的ADC药物制造新方法。与以前的方法相比，化学治疗药物以一种可繁殖的方式被缚束在抗体上，因此对健康细胞的副作用就更少。他们在抗体的结构上修改了特别位点以促进药物的缚束，同时又不会影响抗体的整体结构或识别癌细胞的能力。
对模式小鼠的研究显示，这种新型ADC药物比传统的ADC药物更有效：只有一半剂量的药物就能杀死同样多的癌细胞。而且，对兔子和猴子来说，它们对这种新型的ADC药物具有更好的耐受性，意味着这种药物对人有更小的副作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Biotechnology，doi:10.1038/nbt.1480，Jagath R Junutula，William Mallet
Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
Jagath R Junutula1, Helga Raab1, Suzanna Clark1, Sunil Bhakta1, Douglas D Leipold1, Sylvia Weir1, Yvonne Chen1, Michelle Simpson1, Siao Ping Tsai1, Mark S Dennis1, Yanmei Lu1, Y Gloria Meng1, Carl Ng1, Jihong Yang1, Chien C Lee1, Eileen Duenas1, Jeffrey Gorrell1, Viswanatham Katta1, Amy Kim1, Kevin McDorman1,2, Kelly Flagella1, Rayna Venook1, Sarajane Ross1, Susan D Spencer1, Wai Lee Wong1, Henry B Lowman1, Richard Vandlen1, Mark X Sliwkowski1, Richard H Scheller1, Paul Polakis1 & William Mallet1
AbstractAntibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of potent cytotoxic drugs. However, conventional drug conjugation strategies yield heterogenous conjugates with relatively narrow therapeutic index (maximum tolerated dose/curative dose). Using leads from our previously described phage display–based method to predict suitable conjugation sites, we engineered cysteine substitutions at positions on light and heavy chains that provide reactive thiol groups and do not perturb immunoglobulin folding and assembly, or alter antigen binding. When conjugated to monomethyl auristatin E, an antibody against the ovarian cancer antigen MUC16 is as efficacious as a conventional conjugate in mouse xenograft models. Moreover, it is tolerated at higher doses in rats and cynomolgus monkeys than the same conjugate prepared by conventional approaches. The favorable in vivo properties of the near-homogenous composition of this conjugate suggest that our strategy offers a general approach to retaining the antitumor efficacy of antibody-drug conjugates, while minimizing their systemic toxicity.
1 Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
2 present address: Division of Pathology, Charles River Preclinical Services, Nevada, 6995 Longley Lane, Reno, Nevada 89511, USA.
