Oncolytic Vaccinia Virus-HSP70-shRNA Amplifies Viral Replication, ROS/Autophagy, and Immunity to Fight Colorectal...

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Molecular oncology

Background:

• Colorectal cancer (CRC) remains a leading cause of cancer mortality.
• Immunotherapy efficacy is limited in "cold" tumors, necessitating novel therapeutic strategies.

Purpose of the Study:

• To engineer an oncolytic vaccinia virus (oncoVV-shHSP70) for enhanced efficacy against CRC.
• To investigate the mechanisms underlying oncoVV-shHSP70's oncolytic and immunomodulatory effects.

Main Methods:

• Engineered oncolytic vaccinia virus (oncoVV-shHSP70) expressing HSP70 shRNA.
• In vitro studies on CRC cells assessing apoptosis, ROS, autophagy, and cytokine release.
• In vivo studies using xenograft mouse models to evaluate tumor growth inhibition.

Main Results:

• OncoVV-shHSP70 suppressed HSP70, enhanced viral replication, and induced apoptosis in CRC cells.
• The virus triggered ROS accumulation and stimulated autophagy, creating a synergistic oncolytic effect.
• OncoVV-shHSP70 promoted T-cell and dendritic-cell infiltration, inducing immunogenic cell death and inhibiting tumor growth in vivo.

Conclusions:

• OncoVV-shHSP70 demonstrates potent multimodal therapeutic potential for colorectal cancer.
• The engineered virus overcomes therapeutic resistance through viral oncolysis, apoptosis induction, and immunomodulation.
• OncoVV-shHSP70 represents a promising strategy for enhancing antitumor immunity in CRC.