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Bioorthogonal optimized virus immuno-nanomedicine (BOVIN).

Wenchang Peng1,2,3, Yajing Du1,2, Luna Cui1,2

  • 1School of Life Sciences, Tianjin University, Tianjin, China.

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|November 25, 2025
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Summary

This study introduces bioorthogonal optimized virus immuno-nanomedicine (BOVIN) to combat solid tumors. BOVIN enhances anti-tumor immunity by inducing immunogenic cell death and boosting T-cell responses, offering a novel cancer immunotherapy.

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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.