Antibody-drug conjugates (ADCs) are an emerging class of biopharmaceutical products for oncology, with the cytotoxic pyrrolobenzodiazepine (PBD) family of "warheads" well-established in the clinic. While PBDs offer high potency, they are also characterized by their hydrophobicity, which can make formulation of the ADC challenging. Several approaches have been investigated to improve the physicochemical properties of PBD-containing ADCs, and herein a supramolecular approach was explored using cucurbit[8]uril (CB[8]). The ability of CB[8] to simultaneously encapsulate two guests was exploited to incorporate a 12-mer polyethylene glycol harboring a methyl viologen moiety at one terminus (MV-PEG12), together with a PBD harboring an indole moiety at the C2' position (SG3811). This formulation approach successfully introduced a hydrophilic PEG to mask the hydrophobicity of SG3811, improving the physical stability of the ADC while avoiding any loss of potency related to chemical modification.

中文翻译：

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使用宿主-客体化学方法改善抗体-药物偶联物的物理稳定性。

抗体-药物偶联物（ADCs）是一类新兴的肿瘤生物药物，具有临床上公认的具有细胞毒性的吡咯并苯二氮杂（PBD）“弹头”家族。虽然PBD具有很高的效力，但它们的特征还在于疏水性，这可能会使ADC的配方具有挑战性。已经研究了几种方法来改善含PBD的ADC的理化特性，在此我们使用葫芦[8] uril（CB [8]）探索了一种超分子方法。利用CB [8]同时包封两个客体的能力，将在一个末端带有甲基紫精部分的12-聚乙二醇（MV-PEG12）与在C2'位置带有吲哚部分的PBD结合在一起（ SG3811）。