Cancer-Killing Duo Hunts Down and Destroys Tumors

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.

Surprisingly, bacteria may cause June to reconsider-the new approach has potential as a universal treatment for all sorts of solid tumors.

The molecular tag only sticks to the regions immediately surrounding a tumor and spares healthy cells from CAR T attacks.

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. 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. 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. 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.

Many blood cancers have a universal antigen that signals “I’m cancerous,” making it relatively easy to engineer CAR T cells to find them.

In contrast, have a wide variety of antigens-many of which are also present in normal tissues-lowering CAR T cell efficiency and increasing the chances of deadly side effects.

Even worse, cancer cells pump out glue-like proteins that build a protective shield around cancers. Called the tumor microenvironment, the barrier is highly toxic to CAR T cells.

Its low oxygen levels readily destroy the membranes of CAR T cells. Like popped balloons, the cells spill their contents into surrounding areas, in turn driving inflammation.

Tumors coated in this designer antigen make them easy to spot and vulnerable to CAR T cells designed to destroy them. In a proof of concept, the tag-team system reduced cancer growth and increased survival in mice with an aggressive blood cancer.

Treated mice happily went about their day and maintained a healthy body weight as their tumors shrank. The engineered bacteria lingered near the tumors for at least two weeks.

A dose of bacteria followed by two doses of CAR T cells reduced tumor size four-fold 22 days after treatment. To give the system a boost, the team added another genetic circuit into the bacteria, allowing them to release a chemical that attracts CAR T cells.

The improved method reduced tumors in mice with breast cancer after two shots into the bloodstream.

“Combining the advantages of tumor-homing bacteria and CAR-T cells provides a new strategy for tumor recognition, and this builds the foundation for engineered communities of living therapies,” said study author Rosa Vincent, at Columbia University.

The strategy could be especially powerful in tumors without obvious antigens.

While a low estimate for multiple types of cancers, that’s still “20- to 40-fold larger than the mouse tumors in this study,” said Bressier and Wong.