High-throughput screening to enhance oncolytic virus immunotherapy

Area of Science:

• Oncology
• Virology
• Biotechnology

Background:

• Oncolytic viruses (OVs) are promising biotherapeutics for cancer treatment, with platforms like herpes simplex virus, reovirus, and vaccinia virus showing success in clinical trials.
• Current OV engineering primarily focuses on tumor specificity, with limited manipulation of other factors influencing therapeutic outcomes.
• Key parameters for improving OV efficacy include viral delivery, infectivity, productivity, oncolysis, bystander killing, spread, persistence, immune system engagement, and tumor microenvironment modulation.

Purpose of the Study:

• To review chemical- and genome-based high-throughput screens used to enhance OV therapeutic efficacy.
• To analyze the impact of these screens on OV-mediated cancer treatment.
• To identify emerging themes and future research directions in OV engineering.

Main Methods:

• Review of literature on high-throughput screening methodologies (chemical and genomic) applied to oncolytic viruses.
• Analysis of studies reporting modifications to OV parameters (viral and host levels) and their effects on therapeutic outcomes.
• Synthesis of findings to identify trends and future research opportunities.

Main Results:

• High-throughput screens offer powerful tools for optimizing OV properties such as tumor targeting, replication, and immune modulation.
• Engineering efforts have successfully improved viral delivery, oncolysis, and immune engagement, leading to enhanced therapeutic efficacy in preclinical and clinical settings.
• Significant advancements have been made in manipulating both viral and host factors to improve OV performance.

Conclusions:

• High-throughput screening is crucial for accelerating the development of more effective oncolytic virus therapies.
• Future research should focus on integrated approaches combining viral engineering with host-directed strategies to maximize therapeutic potential.
• Continued exploration of novel screening platforms and engineering targets will be vital for overcoming current limitations in OV therapy.