Translatable drug-loaded iron oxide nanophore sensitizes murine melanoma tumors to monoclonal antibody immunotherapy Journal Article
| Authors: | Stater, E. P.; Morcos, G.; Isaac, E.; Ogirala, A.; Hsu, H. T.; Longo, V. A.; Grimm, J. |
| Article Title: | Translatable drug-loaded iron oxide nanophore sensitizes murine melanoma tumors to monoclonal antibody immunotherapy |
| Abstract: | 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. © 2023 American Chemical Society |
| Keywords: | mouse; animal; animals; mice; cell death; cancer immunotherapy; melanoma; oncology; monoclonal antibodies; monoclonal antibody; antibodies, monoclonal; immunotherapy; tumors; macrophages; dermatology; diseases; mri; chemical modification; drug delivery; iron oxide nanoparticle; iron oxides; ferric oxide; metal nanoparticles; pharmaceutical preparations; drug; targeted drug delivery; ferumoxytol; immune cells; lipid a; controlled drug delivery; iron oxide nanoparticles; magnetite; cell-be; cell/b.e; cell/be; melanoma tumours; ferrosoferric oxide |
| Journal Title: | ACS Nano |
| Volume: | 17 |
| Issue: | 7 |
| ISSN: | 1936-0851 |
| Publisher: | American Chemical Society |
| Date Published: | 2023-04-11 |
| Start Page: | 6178 |
| End Page: | 6192 |
| Language: | English |
| DOI: | 10.1021/acsnano.2c05800 |
| PUBMED: | 36971591 |
| PROVIDER: | scopus |
| PMCID: | PMC10324163 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK author Jan Grimm -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work