Tumors Under Seige by Cancer-Killing Salmonella

Salmonella is a genus of rod-shaped bacteria, often given a bad rap thanks to its association with food poisoning.

But could salmonella also be our ally in the battle against cancer? Yes, say cancer researchers at the University of Missouri, who have created a safe, genetically-engineered strain of the bacteria that selectively swarms into tumors and directs the body’s immune system while delivering anticancer drugs to eliminate the cancerous masses.

Microscopic analyses of cancerous tissues have revealed an interesting phenomenon—T cells that are supposed to destroy cancer cells instead coexist peacefully with them, mistaking the cancer cells for healthy tissues. 

“Normal cells put up a ‘don’t-eat-me’ molecular flag that is recognized by immune cells, thereby preventing destruction of normal tissues,” explained Yves Chabu, the lead researcher on the study. “But some cancers have also developed the ability to mimic normal cells and produce this ‘don’t eat me’ signal. As a consequence, the immune system fails to recognize the cancer as a defective tissue and leaves it alone, which is bad news for the patient.”

Chabu and team hypothesized that bacteria could help unmask these dangerous malignancies hiding in plain sight. 

“Imagine a patient whose cancer isn’t responding to traditional therapies and has no other treatment options,” said Chabu.

“One can envision genetically modifying the bacteria such that it can unload therapeutics that specifically exploit that cancer’s unique vulnerabilities and kill it.” This hypothesis led Chabu and colleagues to the development of the cancer-killing salmonella strain called CRC2631. Amazingly, the origins of this strain stem from a sample of salmonella that had been stored at room temperature for over 50 years. 

The team is now testing CRC2631’s potential as a weapon against cancers. These are a huge step-up from conventional chemotherapeutic approaches; bombarding the body with chemicals that non-specifically destroy any dividing cells generates many unintended side effects.

Cancer-swarming bacteria are different, says Chabu. “Because CRC2631 preferentially colonizes tumor cells, the effect is mainly localized to the tumor.” 

Previous efforts to genetically engineer bacterial species that can achieve this cancer-specific cell killing have not always been successful, with ongoing struggles around safety and efficacy thwarting progress.

“The use of CRC2631 to design and deliver patient-tailored therapeutics foretells potential in precision medicine, or the ability to tailor a treatment to a specific patient,” said Chabu, who together with his team, continues to drive CRC2631 towards clinical translation.

Sources: University of Missouri, Oncotarget.