| Autor: |
Stater EP; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.; Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, United States., Morcos G; University of Pennsylvania, Philadelphia, Pennsylvania 19104-6243, United States., Isaac E; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.; Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, United States., Ogirala A; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States., Hsu HT; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States., Longo VA; Small Animal Imaging Core Facility, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York 10065, United States., Grimm J; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.; Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, United States.; Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York 10065, United States. |
| Abstrakt: |
Macrophages comprise a significant portion of the immune cell compartment within tumors and are known contributors to tumor pathology; however, cancer immunotherapies targeting these cells are not clinically available. The iron oxide nanoparticle, ferumoxytol (FH), may be utilized as a nanophore for drug delivery to tumor-associated macrophages. We have demonstrated that a vaccine adjuvant, monophosphoryl lipid A (MPLA), can be stably captured within the carbohydrate shell of ferumoxytol without chemical modification of either the drug or the nanophore. This drug-nanoparticle combination (FH-MPLA) activated macrophages to an antitumorigenic phenotype at clinically relevant concentrations. In the immunotherapy-resistant B16-F10 model of murine melanoma, FH-MPLA treatment induced tumor necrosis and regression in combination with agonistic α-CD40 monoclonal antibody therapy. FH-MPLA, composed of clinically approved nanoparticle and drug payload, represents a potential cancer immunotherapy with translational relevance. FH-MPLA may be useful as an adjunctive therapy to existing antibody-based cancer immunotherapies which target only lymphocytic cells, reshaping the tumor immune environment. |
