Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, via G. Ripamonti 435, 20141, Milan, Italy.
Department of Oncology and Haematology, University of Milan, Milan, Italy.
Curr Oncol Rep. 2022 Jul;24(7):809-817. doi: 10.1007/s11912-022-01266-4. Epub 2022 Mar 19.
Summarizing the current preclinical and clinical evidence about bystander effect of antibody-drug conjugates (ADCs) in solid tumors.
One of the main challenges of treating solid tumors with ADCs is the heterogeneous expression of the target antigen (Ag), which however may be overcome by the so-called bystander killing effect. This unique, but still debated, feature of certain ADCs is represented by the unintentional payload diffusion from Ag-positive tumor cells to adjacent Ag-negative tumor cells. Some pharmacological characteristics, such as a hydrophobic payload or a cleavable linker, seem to play a major role in this effect. Abundant preclinical evidence of the bystander effect has emerged, and the clinical activity of ADCs in tumors with a heterogeneous Ag expression suggests the relevance of this feature. Additional studies are required to investigate if the bystander effect is necessary for achieving a solid activity with ADCs.
抗体药物偶联物（ADC）在实体瘤中旁观者效应的临床前和临床证据。
用 ADC 治疗实体瘤的主要挑战之一是靶抗原（Ag）的异质性表达，然而，这种效应可以通过所谓的旁观者杀伤效应来克服。某些 ADC 的这种独特但仍有争议的特征，代表了从 Ag 阳性肿瘤细胞向相邻的 Ag 阴性肿瘤细胞意外扩散有效载荷。一些药理学特性，如疏水性有效载荷或可切割的连接子，似乎在这种效应中起主要作用。大量的旁观者效应的临床前证据已经出现，并且 ADC 在具有异质性 Ag 表达的肿瘤中的临床活性表明了这一特征的相关性。需要进一步的研究来探讨旁观者效应是否是 ADC 获得实体瘤疗效的必要条件。
