Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.
Trends Pharmacol Sci. 2020 Jun;41(6):409-417. doi: 10.1016/j.tips.2020.03.005. Epub 2020 Apr 22.
Therapeutic antibodies have revolutionized modern medicine. At present, antibodies are successfully used for treatment of diverse human diseases, ranging from cancer to viral infections. All clinically approved antibodies rely on highly specific recognition of their target antigen. Antigen-binding promiscuity, binding to autoantigens, and propensity for self-binding (homophilic interaction) are highly undesirable characteristics of antibody drug candidates. Nevertheless, the immune system of all healthy individuals constantly produces and uses large quantities of antibodies that can be classified as inappropriate for development as drugs. Here, I provide arguments that antibodies with 'aberrant' properties have therapeutic potential. They could be useful in certain complex pathological conditions, thus enriching our armamentarium for treatment of human diseases.
治疗性抗体已经彻底改变了现代医学。目前，抗体已成功地用于治疗从癌症到病毒感染等多种人类疾病。所有临床批准的抗体都依赖于对其靶抗原的高度特异性识别。抗原结合的混杂性、与自身抗原的结合以及自身结合的倾向（同亲相互作用）是抗体候选药物极不理想的特性。然而，所有健康个体的免疫系统都在不断地产生和使用大量的抗体，这些抗体可以被归类为不适合开发成药物。在这里，我提供了一些论据，表明具有“异常”特性的抗体具有治疗潜力。它们可能在某些复杂的病理情况下有用，从而丰富了我们治疗人类疾病的手段。
