Programmed cell death-ligand 1 (PD-L1) blockers have advanced immunotherapy, but their lack of tumour homing capability represents a substantial challenge. Here we show that genetically engineered filamentous phages can be used as tumour-targeting immunotherapeutic agents that reduce the side effects caused by untargeted delivery of PD-L1 blockers. Specifically, we improved biopanning to discover a peptide binding the extracellular domain of PD-L1 and another targeting both melanoma tissues and cancer cells. The two peptides were genetically fused to the sidewall protein and tip protein of fd phages, respectively. The intravenously injected phages homed to tumours and bound PD-L1 on cancer cells, effectively blocking PD-1/PD-L1 recognition to trigger targeted immunotherapy without body weight loss, organ abnormalities and haematological aberrations. The phages, cost-effectively replicated by bacteria, are cancer-targeting immunotherapeutic nanofibres that can be flexibly designed to target different cancer types and immune checkpoints.

程序性细胞死亡配体 1 （PD-L1） 阻滞剂具有先进的免疫疗法，但它们缺乏肿瘤归巢能力是一个重大挑战。在这里，我们表明基因工程丝状噬菌体可用作肿瘤靶向免疫治疗剂，以减少 PD-L1 阻滞剂非靶向递送引起的副作用。具体来说，我们改进了生物淘选，发现了一种结合 PD-L1 细胞外结构域的肽和另一种靶向黑色素瘤组织和癌细胞的肽。这两个肽分别与 fd 噬菌体的侧壁蛋白和 tip 蛋白进行基因融合。静脉注射的噬菌体位于肿瘤上，并与 PD-L1 结合癌细胞，有效阻断 PD-1/PD-L1 识别以触发靶向免疫治疗，而不会出现体重减轻、器官异常和血液学畸变。噬菌体是靶向癌症的免疫治疗纳米纤维，可通过细菌经济高效地复制，可灵活设计以靶向不同的癌症类型和免疫检查点。