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Article

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

1
Department of Pathology, The Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
2
Department of Surgery, The Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
3
Clinical Bioinformatics Unit, Department of Pathology, The Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
4
Department of Neurology, Clinical and Cancer Proteomics, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
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Department of Viroscience, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Gabriella D’Orazi
Cancers 2021, 13(12), 2896; https://doi.org/10.3390/cancers13122896
Received: 6 May 2021 / Revised: 31 May 2021 / Accepted: 2 June 2021 / Published: 9 June 2021
(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
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, a Toll-like receptor 3 (TLR3) agonist, on human epithelial cancerous cells. Our results demonstrated that Rintatolimod stimulated an anti-viral effect by producing RNase L that blocks virus replication. Moreover, Rintatolimod activated the innate and the adaptive immune systems by activating a cascade of actions in human cancerous cells. We believe that Rintatolimod should be considered in the treatment regimens of cancer patients who suffer from SARS-CoV-2 infection.
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. View Full-Text
Keywords: SARS-CoV-2; Rintatolimod; Toll-like receptor 3; epithelial cancerous cells; RNase L; interferon signaling; cytokines SARS-CoV-2; Rintatolimod; Toll-like receptor 3; epithelial cancerous cells; RNase L; interferon signaling; cytokines
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MDPI and ACS Style

Mustafa, D.A.M.; Saida, L.; Latifi, D.; Wismans, L.V.; de Koning, W.; Zeneyedpour, L.; Luider, T.M.; van den Hoogen, B.; van Eijck, C.H.J. Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients? Cancers 2021, 13, 2896. https://doi.org/10.3390/cancers13122896

AMA Style

Mustafa DAM, Saida L, Latifi D, Wismans LV, de Koning W, Zeneyedpour L, Luider TM, van den Hoogen B, van Eijck CHJ. Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients? Cancers. 2021; 13(12):2896. https://doi.org/10.3390/cancers13122896

Chicago/Turabian Style

Mustafa, Dana A.M., Lawlaw Saida, Diba Latifi, Leonoor V. Wismans, Willem de Koning, Lona Zeneyedpour, Theo M. Luider, Bernadette van den Hoogen, and Casper H.J. van Eijck 2021. "Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients?" Cancers 13, no. 12: 2896. https://doi.org/10.3390/cancers13122896

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