This cancer-targeting Salmonella platform delivers therapeutic proteins directly to cancer tissue, reducing the growth of a tumor or regressing it. Cancer ranks as the second most common cause of death in the United States. Bacteria have been used to target cancers for over 100 years and interest in bacterial-based therapeutics is accelerating because of their unique ability to infiltrate solid tumors and deliver biologics directly within the tumor microenvironment. This targeted approach helps overcome longstanding challenges of traditional therapies, including poor therapeutic stability, systemic toxicity, and limited penetration into tumor tissue.
S. typhimurium, known as salmonella, has strong anti-cancer abilities. It can survive and grow in anoxic regions as wall as in viable oxygenic regions of tumors. It also can identify and penetrate tumors by detecting small molecules such as serine and aspartate. Additionally, Salmonella is easily genetically manipulated while retaining their tumor-targeting and natural tumor-regressing capabilities. These capabilities make Salmonella a widely investigated anti-cancer agent. However, most previous work has used strains derived from strains with inferior abilities to be invasive into tumors compared to strains developed at the University of Florida.
Researchers at the University of Florida have developed cancer-targeting Salmonella strains for the treatment of cancer or other diseases. Via l multiple mucosal and/or parenteral routes of administration, these engineered strains successfully deliver and express proteins, including immune-activating cytokines and photodynamic therapy agents, at concentrations high enough to induce biological effects. These engineered bacteria can eliminate non-targeted distribution, express therapeutic proteins within tumors, and stimulate strong immune responses. They have also been modified to cause very limited adverse effects on normal tissues. These approaches enhance precision while reducing off-target toxicity, offering a safer and more effective method for cancer-targeted delivery.
Tumor-targeting Salmonella strains for delivering therapeutic agents and stimulating immune responses for cancer treatment
Salmonella Typhimurium naturally accumulates in tumors, but unmodified strains lack sufficient efficacy and pose safety concerns. To address this, UF researchers engineered “Cancer Cell Targeting Salmonella (CCTS)” strains with precise deletions and insertions in their genomes. These modifications enable the bacteria to directly destroy tumor cells through their inherent toxicity, while also delivering therapeutic proteins such as cytokines, cytotoxic agents, or immune checkpoint inhibitors. In addition, the strains can carry DNA vaccines that are expressed by tumor cells, creating further antitumor activity. Importantly, the bacteria are designed to self-destruct after completing their task, preventing uncontrolled growth in the body. By combining tumor-targeting capacity with immune stimulation, CCTS strains function as both direct therapeutics and potent adjuvants, and the system can be tailored to different cancers by altering the surface display of adhesins to tumor-specific receptors to deliver various proteins or DNA-encoding cargos.
