Synergistic antitumor mechanisms of combining oncolytic viruses with CAR-based cell therapy (IMAGE)
Caption
The schematic illustrates the dynamic, multistep engineered circuit established by combining oncolytic viruses (OV) and chimeric antigen receptor (CAR)-based cell therapies to overcome solid tumor resistance. (1) Oncolytic virus infection and tumor cell lysis: OVs selectively infect and replicate within tumor cells, triggering immunogenic cell death (ICD). This lytic cycle releases a potent array of tumor-associated antigens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) such as ATP, HMGB1, calreticulin, and dsDNA/RNA. (2) Tumor microenvironment remodeling and immune activation: The released danger signals activate local antigen-presenting cells (APC) and induce robust inflammatory cytokine and chemokine gradients. This shifts the tumor microenvironment (TME) from a suppressive state to an active site of immune amplification. (3) CAR-based immune cells target and eliminate tumor cells: This remodeled microenvironment improves the trafficking, infiltration, and recognition capabilities of transferred CAR-T and CAR-NK cells. As CAR-immune-cells selectively eliminate targets, they work in tandem with viral oncolysis to drive a self-amplifying cycle of coordinated killing, bystander clearance, and durable antitumor immunity. Generated using BioRender.
Credit
Professor Yanhong Shi from City of Hope National Medical Center, USA | https://link.springer.com/article/10.1007/s44466-026-00055-z
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Credit must be given to the creator.
License
CC BY