Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?

Area of Science:

• Oncology
• Gene Therapy
• Virology

Background:

• Gene therapy, synthetic biology, and cancer genomics advancements enable novel viral vector strategies for human cancers.
• Developing precision-engineered viruses requires novel capsids, synthetic promoters, and therapeutic payloads.
• Current research focuses on engineering cancer selectivity into viral vectors at both cell-extrinsic and cell-intrinsic levels.

Purpose of the Study:

• To review opportunities for engineering cancer selectivity into viral vectors.
• To explore the potential of tumor-targeted vectors as platforms for delivering therapeutic transgenes, including immunotherapies.
• To discuss the importance of advanced primary human cellular models for screening novel viral vector candidates.

Main Methods:

• Rational design, pooled library screening, and directed evolution for developing novel viral vectors.
• Utilizing advanced primary human cellular models, such as patient-derived cultures and organoids, for screening.
• Assessing novel capsids, synthetic promoters, and therapeutic payloads for enhanced cancer targeting and efficacy.

Main Results:

• Stringently tumor-targeted vectors can serve as platforms for potent therapeutic transgenes, including immunotherapeutic payloads.
• Immunotherapy payloads can eradicate non-transduced cells by stimulating systemic anticancer immune responses.
• Advanced cellular models facilitate rapid screening and triage of novel viral vector candidates.

Conclusions:

• The combination of improved viral delivery and selectivity, novel capsids and promoters, and potent immunotherapy payloads holds promise for innovative gene therapies in oncology.
• Engineering cancer selectivity into viral vectors is crucial for effective and safe cancer treatment.
• The development of precision-engineered viruses represents a significant step towards delivering novel gene therapies for human cancers.