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A nanoparticle boost for radiotherapy and immunotherapy

Ralph Weichselbaum
Wenbin Lin
Kaiting Yang

A team led by Ludwig Chicago’s Ralph Weichselbaum, Wenbin Lin and Kaiting Yang published a paper in Nature Nanotechnology in late October describing a novel nanoparticle that triggers potent therapeutic immune responses in mouse models of multiple cancers. Named ZnCDA, the nanoparticle is loaded with a drug that activates STING, a protein central to the efficient induction of anti-cancer immunity. STING detects DNA fragments in the cytoplasm that can be generated by infection, radiotherapy and certain chemotherapies. The researchers show that ZnCDA enhances its own accumulation in tumors because STING activation in the cells that line tumor blood vessels disrupts the tumor vasculature. In the tumor, they report, the nanoparticles activate a specific subset of macrophages, pushing them toward a cancer cell-targeting (M1) phenotypic state and enhancing their ability to activate tumor-targeting T cells. A single dose of the nanoparticles suppressed tumor growth in mouse models of colon cancer and of colon cancer metastasis to the liver. ZnCDA also extended survival in a model of B cell lymphoma, suppressed tumors in melanoma and prostate cancer models and induced anti-tumor effects in a model of a type of lung cancer that resists STING activators. Its use in combination with radiotherapy and anti-PD-L1 therapy significantly extended survival in mouse models of pancreatic cancer and glioblastoma, both of which are “cold” tumors and thus typically impervious to immunotherapy.

Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration
Nature Nanotechnology, 2022 October 27

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