Researchers at Columbia Engineering have designed a cancer therapy that enlists both bacteria and viruses to attack tumors. The system, described in Nature Biomedical Engineering, packages an oncolytic virus inside tumor-seeking Salmonella typhimurium, allowing it to bypass immune defenses and release its payload directly in cancer cells.
The approach, called CAPPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), exploits two natural tendencies: bacteria’s ability to migrate to low-oxygen tumor environments and viruses’ preference for infecting malignant cells. Tal Danino, who led the work with colleagues at Columbia and Charles Rice at The Rockefeller University, called it “probably our most technically advanced and novel platform to date.”
One of the challenges in oncolytic virotherapy is pre-existing immunity, which can neutralize therapeutic viruses before they reach tumors. “The bacteria act as an invisibility cloak, hiding the virus from circulating antibodies, and ferrying the virus to where it is needed,” said co-lead author Zakary Singer. Once inside tumor cells, the bacteria lyse and release the viral genome, enabling it to spread among cancer cells.
To control viral spread beyond tumors, the researchers engineered a dependency on a bacterial protease required for viral maturation. “Spreadable viral particles could only form in the vicinity of bacteria, which are needed to provide special machinery essential for viral maturation,” Singer explained.
In mouse studies, the system limited viral activity to tumor sites, supporting its potential for clinical translation. Co-lead author Jonathan Pabón emphasized the broader goal: “As a physician-scientist, my goal is to bring living medicines into the clinic.”
Publication Details
Singer, Z.S., Pabón, J., Huang, H. et al. Engineered bacteria launch and control an oncolytic virus. Nat. Biomed. Eng (2025). https://doi.org/10.1038/s41551-025-01476-8
The approach, called CAPPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), exploits two natural tendencies: bacteria’s ability to migrate to low-oxygen tumor environments and viruses’ preference for infecting malignant cells. Tal Danino, who led the work with colleagues at Columbia and Charles Rice at The Rockefeller University, called it “probably our most technically advanced and novel platform to date.”
One of the challenges in oncolytic virotherapy is pre-existing immunity, which can neutralize therapeutic viruses before they reach tumors. “The bacteria act as an invisibility cloak, hiding the virus from circulating antibodies, and ferrying the virus to where it is needed,” said co-lead author Zakary Singer. Once inside tumor cells, the bacteria lyse and release the viral genome, enabling it to spread among cancer cells.
To control viral spread beyond tumors, the researchers engineered a dependency on a bacterial protease required for viral maturation. “Spreadable viral particles could only form in the vicinity of bacteria, which are needed to provide special machinery essential for viral maturation,” Singer explained.
In mouse studies, the system limited viral activity to tumor sites, supporting its potential for clinical translation. Co-lead author Jonathan Pabón emphasized the broader goal: “As a physician-scientist, my goal is to bring living medicines into the clinic.”
Publication Details
Singer, Z.S., Pabón, J., Huang, H. et al. Engineered bacteria launch and control an oncolytic virus. Nat. Biomed. Eng (2025). https://doi.org/10.1038/s41551-025-01476-8