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A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression

Immune-checkpoint blockade (ICB) therapy has changed the clinical outcome of many types of aggressive tumors, but there still remain many cancer patients that do not respond to these treatments. There is an unmet need to develop a feasible clinical therapeutic platform to increase the rate of respon...

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Autores principales: Meraviglia-Crivelli, Daniel, Villanueva, Helena, Menon, Ashwathi Puravankara, Zheleva, Angelina, Moreno, Beatriz, Villalba-Esparza, María, Pastor, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379514/
https://www.ncbi.nlm.nih.gov/pubmed/35991316
http://dx.doi.org/10.1016/j.omtn.2022.07.017
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author Meraviglia-Crivelli, Daniel
Villanueva, Helena
Menon, Ashwathi Puravankara
Zheleva, Angelina
Moreno, Beatriz
Villalba-Esparza, María
Pastor, Fernando
author_facet Meraviglia-Crivelli, Daniel
Villanueva, Helena
Menon, Ashwathi Puravankara
Zheleva, Angelina
Moreno, Beatriz
Villalba-Esparza, María
Pastor, Fernando
author_sort Meraviglia-Crivelli, Daniel
collection PubMed
description Immune-checkpoint blockade (ICB) therapy has changed the clinical outcome of many types of aggressive tumors, but there still remain many cancer patients that do not respond to these treatments. There is an unmet need to develop a feasible clinical therapeutic platform to increase the rate of response to ICB. Here we use a previously described clinically tested aptamer (AS1411) conjugated with SMG1 RNAi (AS1411-SMG1 aptamer-linked siRNA chimeras [AsiCs]) to inhibit the nonsense-mediated RNA decay pathway inducing tumor inflammation and improving response to ICB. The aptamer AS1411 shows binding to numerous mouse and human tumor cell lines tested. AS1411 induces tumor cytotoxicity in long incubation times, which allows for the use of the aptamer as a carrier to target the RNAi inhibition to the tumor. The AS1411-SMG1 AsiCs induce a strong antitumor response in local and systemic treatment in different types of tumors. Finally, AS1411-SMG1 AsiCs are well tolerated with no detected side effects.
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spelling pubmed-93795142022-08-18 A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression Meraviglia-Crivelli, Daniel Villanueva, Helena Menon, Ashwathi Puravankara Zheleva, Angelina Moreno, Beatriz Villalba-Esparza, María Pastor, Fernando Mol Ther Nucleic Acids Original Article Immune-checkpoint blockade (ICB) therapy has changed the clinical outcome of many types of aggressive tumors, but there still remain many cancer patients that do not respond to these treatments. There is an unmet need to develop a feasible clinical therapeutic platform to increase the rate of response to ICB. Here we use a previously described clinically tested aptamer (AS1411) conjugated with SMG1 RNAi (AS1411-SMG1 aptamer-linked siRNA chimeras [AsiCs]) to inhibit the nonsense-mediated RNA decay pathway inducing tumor inflammation and improving response to ICB. The aptamer AS1411 shows binding to numerous mouse and human tumor cell lines tested. AS1411 induces tumor cytotoxicity in long incubation times, which allows for the use of the aptamer as a carrier to target the RNAi inhibition to the tumor. The AS1411-SMG1 AsiCs induce a strong antitumor response in local and systemic treatment in different types of tumors. Finally, AS1411-SMG1 AsiCs are well tolerated with no detected side effects. American Society of Gene & Cell Therapy 2022-07-20 /pmc/articles/PMC9379514/ /pubmed/35991316 http://dx.doi.org/10.1016/j.omtn.2022.07.017 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Meraviglia-Crivelli, Daniel
Villanueva, Helena
Menon, Ashwathi Puravankara
Zheleva, Angelina
Moreno, Beatriz
Villalba-Esparza, María
Pastor, Fernando
A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title_full A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title_fullStr A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title_full_unstemmed A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title_short A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression
title_sort pan-tumor-sirna aptamer chimera to block nonsense-mediated mrna decay inflames and suppresses tumor progression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379514/
https://www.ncbi.nlm.nih.gov/pubmed/35991316
http://dx.doi.org/10.1016/j.omtn.2022.07.017
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