Quantitative Virus-Associated RNA Detection to Monitor Oncolytic Adenovirus Replication.
Int J Mol Sci
; 25(12)2024 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-38928259
ABSTRACT
Oncolytic adenoviruses are in development as immunotherapeutic agents for solid tumors. Their efficacy is in part dependent on their ability to replicate in tumors. It is, however, difficult to obtain evidence for intratumoral oncolytic adenovirus replication if direct access to the tumor is not possible. Detection of systemic adenovirus DNA, which is sometimes used as a proxy, has limited value because it does not distinguish between the product of intratumoral replication and injected virus that did not replicate. Therefore, we investigated if detection of virus-associated RNA (VA RNA) by RT-qPCR on liquid biopsies could be used as an alternative. We found that VA RNA is expressed in adenovirus-infected cells in a replication-dependent manner and is secreted by these cells in association with extracellular vesicles. This allowed VA RNA detection in the peripheral blood of a preclinical in vivo model carrying adenovirus-injected human tumors and on liquid biopsies from a human clinical trial. Our results confirm that VA RNA detection in liquid biopsies can be used for minimally invasive assessment of oncolytic adenovirus replication in solid tumors in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
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ARN Viral
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Adenoviridae
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Virus Oncolíticos
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Viroterapia Oncolítica
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos