CpG-coated prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma

Juliana Cano-Mejia; Anshi Shukla; Debbie K. Ledezma; Erica Palmer; Alejandro Villagra; Rohan Fernandes

Translational Oncology (Oct 2020)

CpG-coated prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma

Juliana Cano-Mejia,
Anshi Shukla,
Debbie K. Ledezma,
Erica Palmer,
Alejandro Villagra,
Rohan Fernandes

Affiliations

Juliana Cano-Mejia: The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA
Anshi Shukla: The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA
Debbie K. Ledezma: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA; The Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA
Erica Palmer: The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA
Alejandro Villagra: The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA
Rohan Fernandes: The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA; The Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA; Department of Medicine, The George Washington University, Washington, DC 20037, USA; Corresponding author at: The George Washington Cancer Center, The George Washington University, 800 22nd St NW, Science and Engineering Hall, Suite 8410, Washington, DC 20052, USA.

Journal volume & issue: Vol. 13, no. 10
p. 100823

Abstract

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High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a “nanoimmunotherapy,” which combines photothermal therapy (PTT) using CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) combined with anti-CTLA-4 (aCTLA-4) immunotherapy. Our in vitro studies demonstrate that in addition to causing ablative tumor cell death, our nanoimmunotherapy alters the surface levels of co-stimulatory, antigen-presenting, and co-inhibitory molecules on neuroblastoma tumor cells. When administered in a syngeneic, murine model of neuroblastoma bearing synchronous Neuro2a tumors, the CpG-PBNP-PTT plus aCTLA-4 nanoimmunotherapy elicits complete tumor regression in both primary (CpG-PBNP-PTT-treated) and secondary tumors, and long-term survival in a significantly higher proportion (55.5%) of treated-mice compared with the controls. Furthermore, the surviving, nanoimmunotherapy-treated animals reject Neuro2a rechallenge, suggesting that the therapy generates immunological memory. Additionally, the depletion of CD4+, CD8+, and NK+ populations abrogate the observed therapeutic responses of the nanoimmunotherapy. These findings demonstrate the importance of concurrent PTT-based cytotoxicity and the antitumor immune effects of PTT, CpG, and aCTLA-4 in generating a robust abscopal effect against neuroblastoma.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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