Quantitative Virus-Associated RNA Detection to Monitor Oncolytic Adenovirus Replication

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Oncolytic adenoviruses show promise as cancer immunotherapies.
• Assessing intratumoral virus replication is crucial for efficacy but challenging non-invasively.
• Current methods like detecting systemic adenovirus DNA lack specificity for replication.

Purpose of the Study:

• To evaluate virus-associated RNA (VA RNA) detection in liquid biopsies as a marker for oncolytic adenovirus replication.
• To establish a minimally invasive method for monitoring treatment response in solid tumors.

Main Methods:

• Developed and validated RT-qPCR assays for VA RNA detection.
• Investigated VA RNA expression in adenovirus-infected cells.
• Analyzed VA RNA in extracellular vesicles from preclinical models and human clinical trial liquid biopsies.

Main Results:

• VA RNA expression is replication-dependent in infected cells.
• VA RNA is secreted via extracellular vesicles.
• Successfully detected VA RNA in peripheral blood from preclinical models and human trials.

Conclusions:

• VA RNA detection in liquid biopsies is a viable, minimally invasive method.
• This technique allows for assessment of oncolytic adenovirus replication in solid tumors.
• Facilitates monitoring of immunotherapy efficacy in clinical settings.