Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients?

Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastating loss of life. Large registry studies have begun to shed light on the epidemiological and clinical vulnerabilities of cancer patients who succumb to or endure poor outcomes of SARS-CoV-2. Specific treatment for...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (12), p.2896
Main Authors: Mustafa, Dana A. M., Saida, Lawlaw, Latifi, Diba, Wismans, Leonoor V., de Koning, Willem, Zeneyedpour, Lona, Luider, Theo M., van den Hoogen, Bernadette, van Eijck, Casper H. J.
Format: Article
Language:English
Subjects:
Agonists
Angiogenesis
Antiviral agents
Chemokines
Chronic fatigue syndrome
Coronaviruses
COVID-19
Epidemiology
Epithelial cells
Fibrosis
Gene expression
Immune system
Innate immunity
Interferon
Pancreatic cancer
Patients
Proteomics
Ribonuclease L
Severe acute respiratory syndrome coronavirus 2
Signal transduction
TLR3 protein
Toll-like receptors
Viruses
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Summary:Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastating loss of life. Large registry studies have begun to shed light on the epidemiological and clinical vulnerabilities of cancer patients who succumb to or endure poor outcomes of SARS-CoV-2. Specific treatment for COVID-19 infections in cancer patients is lacking while the demand for treatment is increasing. Therefore, we explored the effect of Rintatolimod (Ampligen®) (AIM ImmunoTech, Ocala, FL, USA), a Toll-like receptor 3 (TLR3) agonist, to treat uninfected human pancreatic cancer cells (HPACs). The direct effect of Rintatolimod was measured by targeted gene expression profiling and by proteomics measurements. Our results show that Rintatolimod induces an antiviral effect in HPACs by inducing RNase-L-dependent and independent pathways of the innate immune system. Treatment with Rintatolimod activated the interferon signaling pathway, leading to the overexpression of several cytokines and chemokines in epithelial cells. Furthermore, Rintatolimod treatment increased the expression of angiogenesis-related genes without promoting fibrosis, which is the main cause of death in patients with COVID-19. We conclude that Rintatolimod could be considered an early additional treatment option for cancer patients who are infected with SARS-CoV-2 to prevent the complicated severity of the disease.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13122896