Recombinant Oncolytic Vaccinia Viruses Expressing Human β-Defensin 2 Enhance Anti-tumor Immunity

Area of Science:

• Oncolytic virotherapy
• Immunology
• Cancer research

Background:

• Cancer remains a leading global cause of death.
• Vaccinia virus (VV) is a well-established oncolytic vector due to its safety and efficacy.
• Enhancing the immune response against tumors is crucial for effective cancer therapy.

Purpose of the Study:

• To construct and evaluate a novel recombinant VV expressing human beta-defensin 2 (HBD2).
• To investigate the anti-tumor effects of VV-HBD2-lacZ in a mouse melanoma model.
• To elucidate the underlying mechanisms of immune activation by VV-HBD2-lacZ.

Main Methods:

• Construction of a recombinant VV (VV-HBD2-lacZ) expressing HBD2.
• In vitro and in vivo assessment of HBD2-mediated chemotaxis of dendritic cells (DCs).
• Evaluation of anti-tumor efficacy and immune cell infiltration in a mouse melanoma model.

Main Results:

• VV-HBD2-lacZ demonstrated significant inhibition of tumor growth and metastasis.
• The recombinant virus effectively recruited plasmacytoid DCs (pDCs) to the tumor site.
• Increased infiltration of CD4+ and CD8+ T cells was observed, leading to potent cytotoxic activity.

Conclusions:

• HBD2-expressing VV recruits pDCs, enhancing cytotoxic T-cell responses against tumors.
• Oncolytic VV engineered with HBD2 offers a promising therapeutic strategy by activating innate and adaptive immunity.
• This approach provides an effective treatment for tumors, demonstrating significant in vitro and in vivo anti-tumor effects.