TY - JOUR
T1 - Rintatolimod induces antiviral activities in human pancreatic cancer cells
T2 - Opening for an anti-covid-19 opportunity in cancer patients?
AU - Mustafa, Dana A.M.
AU - Saida, Lawlaw
AU - Latifi, Diba
AU - Wismans, Leonoor V.
AU - de Koning, Willem
AU - Zeneyedpour, Lona
AU - Luider, Theo M.
AU - van den Hoogen, Bernadette
AU - van Eijck, Casper H.J.
N1 - Funding Information:
We thank Support Casper Foundation for financial support for this work (www.sup-portcasper.nl). In addition, this work was supported partially by the fund obtained from ZonMw # 440.20.010.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/9
Y1 - 2021/6/9
N2 - Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastat-ing 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, Flor-ida, 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 overexpres-sion 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 pre-vent the complicated severity of the disease.
AB - Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastat-ing 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, Flor-ida, 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 overexpres-sion 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 pre-vent the complicated severity of the disease.
UR - http://www.scopus.com/inward/record.url?scp=85107395920&partnerID=8YFLogxK
U2 - 10.3390/cancers13122896
DO - 10.3390/cancers13122896
M3 - Article
AN - SCOPUS:85107395920
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 12
M1 - 2896
ER -
