Cancer terminator viruses: Unique conditionally replication competent oncolytic viruses producing therapeutic...

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Adenovirus vector engineering

Background:

• Cancer terminator viruses (CTVs) are engineered oncolytic adenoviruses.
• They utilize cancer-selective promoters (e.g., PEG-3) for tumor-specific replication.
• CTVs are armed with cytokines (e.g., MDA7/IL-24) to enhance anti-cancer effects.

Purpose of the Study:

• To evaluate the efficacy of CTVs in preclinical cancer models.
• To assess the synergistic potential of CTVs with conventional therapies and advanced delivery systems.
• To highlight the clinical translatability of CTVs for solid tumors.

Main Methods:

• Development of chimeric fiber-modified adenoviral backbones (Ad.5/3) for enhanced tumor cell infection.
• Utilizing cancer-selective promoters to restrict viral replication to tumor cells.
• Arming CTVs with immunomodulatory cytokines like MDA7/IL-24 and interferon-gamma.
• Preclinical testing in xenograft models, often combined with chemotherapy, radiotherapy, or immune checkpoint inhibitors.
• Integration with advanced delivery technologies like ultrasound-targeted microbubble destruction.

Main Results:

• CTVs demonstrated eradication of primary and metastatic lesions in multiple xenograft models.
• Significant synergy observed when CTVs were combined with chemotherapy, radiotherapy, and immune checkpoint inhibitors.
• Enhanced infectivity of Ad.5/3 vectors in tumors with low Coxsackie-adenovirus receptor expression.
• Cytokine payloads induced cancer-selective apoptosis, autophagy, and immune responses, including bystander killing.

Conclusions:

• CTVs represent a versatile and clinically translatable viro-immunotherapeutic strategy for advanced solid tumors.
• Ongoing research focuses on incorporating advanced cytokine variants and rational combination therapies.
• CTVs hold promise for improved cancer treatment outcomes in clinical settings.