Journal article
Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8+ T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model
Oncotarget, v 12(4), pp 292-303
16 Feb 2021
PMID: 33659041
Abstract
Background: Esophageal adenocarcinoma (EAC) is a deadly disease with limited treatment options. STING is a transmembrane protein that activates transcription of interferon genes, resulting in stimulation of APCs and enhanced CD8+ T-cell infiltration. The present study evaluates STING agonists, alone and in combination with radiation to determine durable anticancer activity in solid tumors.
Materials and Methods: Esophagojejunostomy was performed on rats to induce reflux leading to the development of EAC. At 32 weeks post operatively, rats received intratumorally either 50 μg STING (ADU-S100) or placebo (PBS), +/– 16Gy radiation. Drug activity was evaluated by pre- and post- treatment MRI, histology, immunofluorescence and RT-PCR.
Results: Mean MRI tumor volume decreased by 30.1% and 50.8% in ADU-S100 and ADU-S100 + radiation animals and increased by 76.7% and 152.4% in placebo and placebo + radiation animals, respectively (
P
< 0.0001). Downstream gene expression, pre- to on- and post- treatment, demonstrated significant upregulation of IFNβ, TNFα, IL-6, and CCL-2 in the treatment groups vs. placebo. On- or post- treatment, radiation alone, ADU-S100 alone, and ADU-S100 + radiation groups demonstrated enhanced PD-LI expression, induced by upregulation of CD8+ T-cells (
p
< 0.01).
Conclusions: ADU-S100 +/– radiation exhibits potent antitumor activity and a promising immunomodulatory profile in a
de novo
EAC.
Metrics
1 Record Views
33 citations in Scopus
Details
- Title
- Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8+ T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model
- Creators
- Ali H. Zaidi - Allegheny Health NetworkRonan J. Kelly - Baylor University Medical CenterAnastasia Gorbunova - Allegheny Health NetworkAshten N. Omstead - Allegheny Health NetworkMadison S. Salvitti - Lung InstitutePing Zheng - Allegheny Health NetworkJuliann E. Kosovec - Allegheny Health NetworkSoyoung Lee - Allegheny Health NetworkShahin Ayazi - Allegheny Health NetworkLaila Babar - Allegheny Health NetworkGene G. Finley - Allegheny Health NetworkAjay Goel - City Of Hope National Medical CenterBlair A. Jobe - Allegheny Health Network
- Publication Details
- Oncotarget, v 12(4), pp 292-303
- Publisher
- Impact Journals LLC
- Number of pages
- 12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Scopus ID
- 2-s2.0-85102442147
- Other Identifier
- 991022048293704721