靶向免疫检查点是癌症治疗中一项行之有效的策略，阻断 PD-1/PD-L1 相互作用以恢复针对癌细胞的免疫活性的抗体已得到临床验证。最近提出了 PD-1 胞外域的高亲和力突变体作为靶向癌细胞上 PD-L1 的抗体的替代品，为这一研究领域带来了新的曙光。在这种动态情况下，本文报道的 PD-1 突变体极大地扩展了非抗体和非小分子抑制剂疗法的化学空间，可用于靶向过度表达 PD-L1 受体的癌细胞。用作位点选择性标签的聚乙二醇部分和刺激免疫反应的碳水化合物代表了未来应用的概念证明。

Targeting immune checkpoints is a well-established strategy in cancer therapy, and antibodies blocking PD-1/PD-L1 interactions to restore the immunological activity against cancer cells have been clinically validated. High-affinity mutants of the PD-1 ectodomain have recently been proposed as an alternative to antibodies to target PD-L1 on cancer cells, shedding new light on this research area. In this dynamic scenario, the PD-1 mutant, here reported, largely expands the chemical space of nonantibody and nonsmall-molecule inhibitor therapeutics that can be used to target cancer cells overexpressing PD-L1 receptors. The polyethylene glycol moieties and the immune response-stimulating carbohydrates, used as site-selective tags, represent the proof of concept for future applications.