ADC Therapeutic Development, Zymeworks Inc., Vancouver, BC, Canada.
Cancer Cell. 2022 Nov 14;40(11):1255-1263. doi: 10.1016/j.ccell.2022.09.016. Epub 2022 Oct 13.
Despite a prevailing dogma wherein antibody drug conjugates (ADCs) increase the maximum tolerated dose of potent cytotoxin payloads while lowering the minimum effective dose, mounting clinical evidence argues that the tolerated doses of ADCs are not significantly different from those of related small molecules. Nonetheless, when dosed at or near the maximum tolerated dose, certain ADCs demonstrate improved efficacy. Understanding the challenges and opportunities for this class of biotherapeutics will help improve the design of next-generation ADCs.
尽管有一种流行的观点认为,抗体药物偶联物(ADC)在降低有效最小剂量的同时增加了有效细胞毒素药物的最大耐受剂量,但越来越多的临床证据表明,ADC 的耐受剂量与相关小分子药物并无显著差异。然而,当 ADC 以最大耐受剂量或接近最大耐受剂量给药时,某些 ADC 显示出改善的疗效。了解这类生物治疗药物的挑战和机遇将有助于改进下一代 ADC 的设计。