Leveraging multimodal cancer immunotherapy to amplify the efficacy of oncolytic viruses

Area of Science:

• Oncology
• Immunotherapy
• Virology

Background:

• Oncolytic viruses (OVs) selectively target and destroy tumor cells, stimulating systemic antitumor immunity.
• Therapeutic efficacy of OVs is often hindered by antiviral immunity, limited spread within tumors, and an immunosuppressive tumor microenvironment.

Purpose of the Study:

• To review emerging strategies for enhancing OV efficacy through combination therapies.
• To explore how synergistic interventions can overcome OV limitations and promote durable antitumor immunity.

Main Methods:

• Review of current research on combining OVs with immune checkpoint inhibitors, adoptive cell therapies, cancer vaccines, and small-molecule immunomodulators.
• Discussion of advanced OV engineering strategies, including transgene delivery and mitigation of host antiviral responses.
• Integration of artificial intelligence and multiomics for patient stratification and regimen optimization.

Main Results:

• Combination therapies can remodel the tumor microenvironment, enhance immune cell activity, and promote immunogenic cell death.
• Synergistic approaches amplify OV replication and potency, leading to improved antitumor responses.
• Advanced engineering and AI-driven insights further bolster OV effectiveness.

Conclusions:

• Multimodal immunotherapy, integrating OVs with complementary strategies, is crucial for overcoming OV limitations.
• Combination approaches are central to OV-based immuno-oncology, paving the way for enhanced clinical translation.
• Future research should focus on optimizing these combination regimens for durable antitumor immunity.