Bioorthogonal optimized virus immuno-nanomedicine (BOVIN)

Area of Science:

• Oncology
• Immunology
• Nanomedicine

Background:

• Tumor immunotherapy often fails due to low tumor cell immunogenicity and immunosuppressive tumor microenvironments.
• Viral infections in cancer patients can stimulate anti-tumor immune responses.
• Developing effective targeted cancer therapies remains a critical challenge.

Purpose of the Study:

• To develop a novel bioorthogonal optimized virus immuno-nanomedicine (BOVIN) for targeted solid tumor therapy.
• To investigate the mechanisms by which BOVIN induces immunogenic cell death (ICD) and enhances anti-tumor immunity.
• To evaluate BOVIN's potential to overcome tumor immunosuppression and improve immunotherapy outcomes.

Main Methods:

• Utilized nonpathogenic recombinant influenza virus (A/WSN/1933(WSN)) as the base for virus immuno-nanomedicine (VIN).
• Engineered WSN with lactate oxidase to produce hydrogen peroxide, enhancing ICD.
• Assessed tumor cell ICD, antigen-presenting cell activation, CD8+ T-cell infiltration, and immune checkpoint blocker sensitivity in vivo.

Main Results:

• BOVIN induced immunogenic cell death (ICD) in tumor cells via mitochondrial stress.
• Surface modification with lactate oxidase synergistically enhanced ICD by consuming lactate and producing hydrogen peroxide.
• BOVIN treatment led to increased antigen-presenting cell activation, significant CD8+ T-cell infiltration, and enhanced sensitivity to immune checkpoint blockers.
• BOVIN activated anti-tumor immune memory, effectively inhibiting tumor recurrence post-surgery.

Conclusions:

• Bioorthogonal nonpathogenic recombinant VIN (BOVIN) effectively reverses tumor-induced immunosuppression.
• BOVIN demonstrates significant potential for enhancing targeted solid tumor immunotherapy.
• This approach offers a promising strategy for improving cancer treatment outcomes and preventing tumor recurrence.