Tuning cellular metabolism for cancer virotherapy

Area of Science:

• Immunology
• Virology
• Metabolic Engineering

Background:

• Oncolytic viruses (OVs) are an emerging immunotherapy for cancer, offering direct tumor lysis and antitumor immunity.
• Challenges such as limited persistence and moderate efficacy require novel strategies for enhanced therapeutic outcomes.

Purpose of the Study:

• To review recent advancements in metabolic reprogramming to enhance OV-based immunotherapies.
• To explore strategies for engineering OVs and combination regimens to optimize tumor and immune cell metabolism.

Main Methods:

• Engineering OVs to target cancer cell metabolic pathways (glycolysis, glutaminolysis, nucleotide synthesis).
• Investigating metabolic rewiring of immune cells (T cells, NK cells) focusing on lipids, amino acids, and carbohydrates.
• Discussing insights for clinical implementation of metabolically enhanced oncolytic platforms.

Main Results:

• Targeting cancer cell metabolism can boost OV replication and tumor cell death.
• Modulating immune cell metabolism shows potential for improved antitumor effects.
• Balancing metabolic interventions is key to promote viral persistence and tumor clearance while limiting antiviral responses.

Conclusions:

• Metabolic remodeling is a promising strategy to enhance the efficacy of OV immunotherapies.
• Further research and clinical translation of metabolically engineered OVs are warranted.
• Optimizing metabolic interventions can overcome current limitations of OV therapy.