Perez Heidi L, Cardarelli Pina M, Deshpande Shrikant, Gangwar Sanjeev, Schroeder Gretchen M, Vite Gregory D, Borzilleri Robert M
Bristol-Myers Squibb Research & Development, Princeton, NJ 08543, USA.
Bristol-Myers Squibb Research & Development, Redwood City, CA 94063, USA.
Drug Discov Today. 2014 Jul;19(7):869-81. doi: 10.1016/j.drudis.2013.11.004. Epub 2013 Nov 15.
Antibody-drug conjugates (ADCs) aim to take advantage of the specificity of monoclonal antibodies (mAbs) to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells. Despite the simple concept, various parameters must be considered when designing optimal ADCs, such as selection of the appropriate antigen target and conjugation method. Each component of the ADC (the antibody, linker and drug) must also be optimized to fully realize the goal of a targeted therapy with improved efficacy and tolerability. Advancements over the past several decades have led to a new generation of ADCs comprising non-immunogenic mAbs, linkers with balanced stability and highly potent cytotoxic agents. Although challenges remain, recent clinical success has generated intense interest in this therapeutic class.
抗体药物偶联物(ADCs)旨在利用单克隆抗体(mAbs)的特异性,将强效细胞毒性药物选择性地递送至表达抗原的肿瘤细胞。尽管概念简单,但在设计最佳ADC时必须考虑各种参数,例如选择合适的抗原靶点和偶联方法。ADC的每个组分(抗体、连接子和药物)也必须进行优化,以充分实现提高疗效和耐受性的靶向治疗目标。过去几十年的进展催生了新一代ADC,其包含非免疫原性单克隆抗体、具有平衡稳定性的连接子和高效细胞毒性药物。尽管挑战依然存在,但近期的临床成功引发了人们对这类疗法的浓厚兴趣。