Translatable Drug-Loaded Iron Oxide Nanophore Sensitizes Murine Melanoma Tumors to Monoclonal Antibody Immunotherapy.
Evan P StaterGeorge MorcosElizabeth IsaacAnuja OgiralaHsiao-Ting HsuValerie A LongoJan GrimmPublished in: ACS nano (2023)
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.
Keyphrases
- iron oxide
- monoclonal antibody
- induced apoptosis
- drug delivery
- papillary thyroid
- cell cycle arrest
- endoplasmic reticulum stress
- cancer therapy
- drug induced
- squamous cell
- early stage
- adverse drug
- oxidative stress
- diabetic rats
- emergency department
- cell proliferation
- high glucose
- combination therapy
- endothelial cells
- risk assessment