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Updated: Jun 10, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Small-Molecule Therapeutics Achieve Multiple Mechanism-Mediated Sensitizations of Colorectal Cancer to Immune
Xiuqi Li1,2, Xuwentai Liu1,2, Meng Wang1,2
1State Key Laboratory of Natural Medicines, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 211198, China.
Abstract:
Immune checkpoint blockade (ICB) therapy has been approved for colorectal cancer (CRC). However, response rates are variable and often <50%. The low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) jointly contribute to this suboptimal response rate. This study confirmed the potential of combining immunogenic cell death (ICD) inducer irinotecan (IRI) and transforming growth factor-β (TGF-β) inhibitor galunisertib (GAL) to improve tumor immunogenicity and remodel the immunosuppressive TME. Moreover, to ameliorate the in vivo delivery barriers associated with small molecules, neutrophil micropharmacies (NOG) were developed for the codelivery of IRI and GAL, which loaded the commercial liposome formulation of IRI (ONIVYDE, ONI) intracellularly and conjugated the pH-responsive GAL liposome (GLP) on the cell surface. This neutrophil-based formulation resulted in a >4-fold increase in the ratios of the amount of both IRI and GAL accumulated in tumors to the dosage administration, effectively achieving multiple mechanism-mediated sensitization of CRC to ICB therapy.
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