基于糖工程化的抗 PD-1-iRGD 肽偶联物通过 T 细胞接合增强抗肿瘤疗效

Despite the important breakthroughs of immune checkpoint inhibitors in recent years, the objective response rates remain limited.

Here, we synthesize programmed cell death protein-1 (PD-1) antibody-iRGD cyclic peptide conjugate (αPD-1-(iRGD) 2 ) through glycoengineering methods.

In addition to enhancing tissue penetration, αPD-1-(iRGD) 2 simultaneously engages tumor cells and PD-1 + T cells via dual targeting, thus mediating tumor-specific T cell activation and proliferation with mild effects on non-specific T cells. In multiple syngeneic mouse models, αPD-1-(iRGD) 2 effectively reduces tumor growth with satisfactory biosafety.

Moreover, results of flow cytometry and single-cell RNA-seq reveal that αPD-1-(iRGD) 2 remodels the tumor microenvironment and expands a population of "better effector" CD8 + tumor infiltrating T cells expressing stem- and memory-associated genes, including Tcf7, Il7r, Lef1, and Bach2. Conclusively, αPD-1-(iRGD) 2 is a promising antibody conjugate therapeutic beyond antibody-drug conjugate for cancer immunotherapy.