GlycoConnect技术可以轻易地适应不同的药物-抗体比（DARs），目前也正在评估包括ADCT-601（DAR2），MRG004a（DAR4）和XMT-1660（DAR6）在内的各种临床计划中。虽然抗体药物偶联物（ADC）通常具有DAR2-8，但已经明确，具有超强有效荷载（例如PBD二聚体和calicheamicin）的ADC只能以低剂量（<0.5 mg/kg）给患者使用，这可能会影响有效的生物分布，并且可能不足以达到肿瘤中目标受体的饱和。在这里，我们展示了GlycoConnect技术可以轻松扩展到DAR1 ADC，而无需重新设计抗体。我们证明了各种超强的细胞毒药物负载都适用于这种方法。在随后的实验中，HCC-1954肿瘤球体分别用标记有AlexaFluor647的DAR1或DAR2 PBD型ADC处理，以研究对肿瘤穿透的影响。与相等的有效荷载剂量相比，DAR1 ADC比DAR2 ADC显示出更显著的肿瘤球体穿透改善，凸显了具有超强有效荷载的ADC具有较低DAR的潜力。

GlycoConnect technology can be readily adapted to provide different drug-to-antibody ratios (DARs) and is currently also evaluated in various clinical programs, including ADCT-601 (DAR2), MRG004a (DAR4), and XMT-1660 (DAR6). While antibody-drug conjugates (ADCs) typically feature a DAR2-8, it has become clear that ADCs with ultrapotent payloads (e.g., PBD dimers and calicheamicin) can only be administered to patients at low doses (<0.5 mg/kg), which may compromise effective biodistribution and may be insufficient to reach target receptor saturation in the tumor. Here, we show that GlycoConnect technology can be readily extended to DAR1 ADCs without the need of antibody re-engineering. We demonstrate that various ultrapotent, cytotoxic payloads are amenable to this methodology. In a follow-up experiment, HCC-1954 tumor spheroids were treated with either an AlexaFluor647-labeled DAR1 or DAR2 PBD-based ADC to study the effect on tumor penetration. Significant improvement of tumor spheroid penetration was observed for the DAR1 ADC compared to the DAR2 ADC at an equal payload dose, underlining the potential of a lower DAR for ADCs bearing ultrapotent payloads.