Filamentous phages as tumour-targeting immunotherapeutic bionanofibres

Abstract

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.