Shaping viral immunotherapy towards cancer-targeted immunological cell death

Area of Science:

• Oncology
• Virology
• Immunology
• Gene Therapy

Background:

• Oncolytic viruses (OVs) selectively target and destroy cancer cells, offering a promising avenue for next-generation cancer therapy.
• OVs induce immunogenic cell death (ICD), initiating the cancer-immunity cycle (CIC) to activate and reshape anti-cancer immunity.
• Genetic engineering of OVs, including the addition of cancer cell-specific binders and immunostimulatory molecules, enhances immune responses and improves virotherapy safety and specificity.

Purpose of the Study:

• To provide an updated review of oncolytic virus immunotherapy.
• To highlight the adaptability of viruses in modulating the tumor immune microenvironment for enhanced anti-cancer treatment.
• To discuss strategies for improving OV tumor specificity and safety.

Main Methods:

• A literature search was conducted on PubMed using terms related to oncolytic viruses, immunotherapy, virotherapy, viral vectors, and gene therapy.
• Retrieved articles included research papers, meta-analyses, and systematic reviews, with no language restrictions.

Main Results:

• Current strategies focus on enhancing OV tumor specificity and safety through various biochemical and genetic modifications.
• Methods discussed include transduction targeting (e.g., xenotype switching, pseudotyping) and non-transduction modifications (e.g., miRNA, optogenetics).
• The review examines mechanisms of ICD and viral modifications that promote cancer cell death and modulate anti-cancer immunity.

Conclusions:

• Immunogenic cell death (ICD) induced by oncolytic viruses is crucial for potent anti-cancer immunity.
• Genetic engineering of OVs with immunostimulatory molecules enhances therapeutic potential, safety, and stability.
• Modifications like deleting apoptosis-inhibiting viral genes can boost ICD, but synergistic effects vary by cancer type.