Deonarain Mahendra P, Xue Quinn
Antikor Biopharma Ltd, Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG12FX, UK.
Essex Biotechnology Ltd, Shun Tak Centre, Room 2818, China Merchants Tower, Connaught Road Central, Hong Kong 168-200, SAR China.
Antib Ther. 2020 Nov 25;3(4):237-245. doi: 10.1093/abt/tbaa024. eCollection 2020 Dec.
The pharmacokinetic-pharmacodynamic relationship is extremely complex and tumour drug penetration is one key parameter influencing therapeutic efficacy. In the context of antibody-drug conjugates (ADCs), which has undergone many innovation cycles and witnessed many failures, this feature is being addressed by a number of alternative technologies. Immunoglobulin-based ADCs continue to dominate the industrial landscape, but smaller formats offer the promise of more-effective cytotoxic payload delivery to solid tumours, with a higher therapeutic window afforded by the more rapid clearance. To make these smaller formats viable as delivery vehicles, a number of strategies are being employed, which will be reviewed here. These include identifying the most-appropriate size to generate the larger therapeutic window, increasing the amount of functional, cytotoxic payload delivered through conjugation or half-life extending technologies or other ways of extending the dosing without inducing toxicity.
药代动力学-药效学关系极为复杂，肿瘤药物渗透是影响治疗效果的一个关键参数。在经历了多个创新周期且见证了诸多失败的抗体药物偶联物（ADC）领域，许多替代技术正在解决这一特性问题。基于免疫球蛋白的ADC在行业格局中继续占据主导地位，但更小的形式有望将更有效的细胞毒性载荷递送至实体瘤，通过更快的清除率提供更高的治疗窗口。为使这些更小的形式成为可行的递送载体，正在采用多种策略，本文将对此进行综述。这些策略包括确定产生更大治疗窗口的最合适尺寸，通过偶联或半衰期延长技术或其他在不诱导毒性的情况下延长给药的方式增加功能性细胞毒性载荷的递送量。
