Genetically Engineered Cell Membrane Nanovesicles for Oncolytic Adenovirus Delivery: A Versatile Platform for Cancer...

Area of Science:

• Oncolytic virotherapy
• Biomaterials science
• Immunology

Background:

• Pre-existing neutralizing antibodies (nAbs) and poor targeting limit systemic oncolytic adenovirus (OA) efficacy.
• Developing strategies to overcome immune evasion and improve tumor selectivity is crucial for OA-based cancer therapy.

Purpose of the Study:

• To design bioengineered cell membrane nanovesicles (BCMNs) for immune shielding and targeted delivery of OA.
• To evaluate the efficacy of OA@BCMNs in preclinical cancer models, assessing immune response, tumor targeting, and therapeutic outcomes.

Main Methods:

• Two biomimetic synthetic approaches were used: in vitro genetic membrane engineering and in vivo CRISPR-mediated expression of targeting ligands on red blood cell membranes.
• Oncolytic adenoviruses were encapsulated within BCMNs (OA@BCMNs).
• In vitro and in vivo studies assessed OA infectivity, replication, immune response suppression, tumor targeting, oncolysis, and survival in xenograft models.

Main Results:

• Both bioengineering approaches maintained OA infectivity and replication in the presence of nAbs, both in vitro and in vivo.
• OA@BCMNs significantly suppressed innate and adaptive immune responses against OA.
• Enhanced tumor targeting, viral oncolysis, and improved survival were observed in xenograft models without significant toxicity.

Conclusions:

• Bioengineered cell membrane nanovesicles (BCMNs) offer a promising strategy to overcome antiviral immunity and enhance cancer cell selectivity for oncolytic virotherapy.
• These biomimetic synthesis approaches provide a potential clinical basis for improving the systemic administration and efficacy of oncolytic adenoviruses.