Mysterious Heroes: Bacteria Join Forces with CAR T to Battle Solid Tumours

Thursday - October 19 2023, 21:17 UTC - 1 year ago

CAR T, or cancer-fighting T-cells, is a revolutionary new approach to treat cancer. In a new study however, it has been discovered that bacteria can be used in a powerful tag-team therapy to fight even the most stubborn solid tumors. The engineered bugs secrete a molecule to draw in nearby CAR T soldiers that destroy tumour cells without damaging the surrounding healthy cells. CAR T has donned super-powers of sorts, and now, with the help of bacteria, cancer may be fighting a losing battle.

Bacteria may seem like a strange ally in the battle against cancer. But in a new study, genetically engineered bacteria were part of a tag-team therapy to shrink tumors. In mice with blood, breast, or colon cancer, the bacteria acted as homing beacons for their partners—modified T cells—as the two sought out and destroyed tumor cells.

CAR T—the name for therapies using these cancer-destroying T cells—is a transformative approach. First approved by the US Food and Drug Administration (FDA) for a type of deadly leukemia in 2017, there are now six treatments available for multiple types of blood cancers. Dubbed a "living drug" by pioneer researcher Dr. Carl June at University of Pennsylvania, CAR T is beginning to take on autoimmune diseases, heart injuries, and liver problems. It is also poised to wipe out senescent "zombie cells" linked to age-related diseases and fight off HIV and other viral infections.

Despite its promise, however, CAR T falters when pitted against solid tumors—which make up roughly 90 percent of all cancers. "Each type of tumor has its own little ways of evading the immune system," said June previously in Penn Medicine News. "So there won’t be one silver-bullet CAR T therapy that targets all types of tumors." .

Surprisingly, bacteria may cause June to reconsider—the new approach has potential as a universal treatment for all sorts of solid tumors. When given to mice, the engineered bugs dug deep into the cores of tumors and readily secreted a synthetic "tag" to draw in nearby CAR T soldiers. The molecular tag only sticks to the regions immediately surrounding a tumor and spares healthy cells from CAR T attacks. The engineered bacteria could also, in theory, infiltrate other types of solid tumors, including "sneaky" ones difficult to target with conventional therapies. Together, the new method called ProCAR—probiotic-guided CAR T cells—combines bacteria and T cells into a cancer-fighting powerhouse. It showcases "the utility of engineered bacteria as a new enhancement to CAR T cell therapy," said Eric Bressler and Dr. Wilson Wong at Boston University, who were not involved in the study.

Hang on, what’s CAR T again? In a nutshell, CAR T therapies use T cells that have been genetically engineered to boost their existing abilities. T cells are already natural born killers that hunt down and destroy viruses, bacteria, and cancers inside our body. They use cellular "claws" to grab onto special proteins on the surfaces of target cells—called antigens—without damaging nearby healthy cells.

But cancer cells are tricky foes. Their antigens rapidly mutate to avoid T cell surveillance and attacks. CAR T therapy overrides this defense by engineering T cells to better seek and destroy their targets. The process usually goes like this. T cells are extracted in a blood draw. Scientists then insert genes into the cells to make a new protein "claw" to grab onto a specific antigen. These engineered cells are infused back into the patient’s body where they hunt down that antigen and destroy the target cell. Recent work is also exploring directly editing T cells inside the body. CAR T has donned super-powers of sorts, and now, with the help of bacteria, cancer may be fighting a losing battle.