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

Abstract：

: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.

journal_name

Transl Oncol

journal_title

Translational oncology

authors

Cano-Mejia J,Shukla A,Ledezma DK,Palmer E,Villagra A,Fernandes R

doi

10.1016/j.tranon.2020.100823

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

100823

issue

10

issn

1936-5233

pii

S1936-5233(20)30315-6

journal_volume

13

pub_type

杂志文章

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