Systemically Administered Sindbis Virus in Combination with Immune Checkpoint Blockade Induces Curative Anti-tumor...

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Tumor immunology

Background:

• Oncolytic viruses are a promising cancer treatment strategy.
• NYESO-1 is a tumor antigen expressed in various cancers, including ovarian cancer.
• Immune checkpoint inhibitors, like anti-PD-1, are crucial in cancer therapy.

Purpose of the Study:

• To investigate Sindbis virus (SV) expressing NYESO-1 (SV-NYESO1) for solid tumor treatment.
• To evaluate the efficacy of SV-NYESO1 combined with anti-PD-1 therapy in a preclinical model.

Main Methods:

• Engineered Sindbis virus (SV-NYESO1) to express the NYESO-1 antigen.
• Treated mice bearing NYESO-1-expressing tumors with SV-NYESO1 and/or anti-PD-1.
• Assessed immune responses, including lymphocyte activation, T cell activity, and myeloid-derived suppressor cells.
• Monitored tumor growth and long-term survival.

Main Results:

• SV-NYESO1 induced a pro-inflammatory environment and systemic lymphocyte activation.
• Combination therapy with SV-NYESO1 and anti-PD-1 significantly enhanced anti-tumor immunity.
• The combined treatment reduced immunosuppressive cells, increased T cell activation, and promoted tumor clearance.
• Complete tumor eradication and long-term protection against recurrence were observed in mice.

Conclusions:

• SV-NYESO1 acts as an immunostimulatory agent, potentiating anti-tumor responses.
• Combined SV-NYESO1 and anti-PD-1 therapy demonstrates significant efficacy against NYESO-1-expressing tumors.
• These findings support clinical investigation of this combination for treating relevant cancers.