Layer-by-layer interleukin-12 nanoparticles drive a safe andeffective response in ovarian tumors
Name
Bioengineering Transla Med - 2022 - Barberio - Layer‐by‐layer interleukin‐12 nanoparticles drive a safe and effective.pdf
Description
Published version
Size
2.31 MB
Format
Adobe PDF
Checksum (MD5)
b363b735fdd4bde0a982ce5b84c6e75f
Author(s)
Barberio, Antonio E
Smith, Sean G
Pires, Ivan S
Iyer, Sonia
Reinhardt, Ferenc
Melo, Mariane B
Suh, Heikyung
Weinberg, Robert A
Irvine, Darrell J
Hammond, Paula T
Date Issued
December 1, 2022
Journal
Bioengineering & Translational Medicine
Publisher
Wiley
Citation
Barberio, Antonio E, Smith, Sean G, Pires, Ivan S, Iyer, Sonia, Reinhardt, Ferenc et al. 2022. "Layer-by-layer interleukin-12 nanoparticles drive a safe andeffective response in ovarian tumors." Bioengineering & Translational Medicine, 8 (2).
Version
Final published version
Abstract
Ovarian cancer is especially deadly, challenging to treat, and has proven refractory to known immunotherapies. Cytokine therapy is an attractive strategy to drive a proinflammatory immune response in immunologically cold tumors such as many high grade ovarian cancers; however, this strategy has been limited in the past due to severe toxicity. We previously demonstrated the use of a layer‐by‐layer (LbL) nanoparticle (NP) delivery vehicle in subcutaneous flank tumors to reduce the toxicity of interleukin‐12 (IL‐12) therapy upon intratumoral injection. However, ovarian cancer cannot be treated by local injection as it presents as dispersed metastases. Herein, we demonstrate the use of systemically delivered LbL NPs using a cancer cell membrane‐binding outer layer to effectively target and engage the adaptive immune system as a treatment in multiple orthotopic ovarian tumor models, including immunologically cold tumors. IL‐12 therapy from systemically delivered LbL NPs shows reduced severe toxicity and maintained anti‐tumor efficacy compared to carrier‐free IL‐12 or layer‐free liposomal NPs leading to a 30% complete survival rate.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Whitehead Institute for Biomedical Research
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
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DOI of Published Version
https://doi.org/10.1002/btm2.10453
