A team at Columbia University School of Engineering and Applied Science has developed a technique to enhance chimeric antigen receptor (CAR) T cell therapy in solid tumors. The technique involves engineering E. coli bacteria, that naturally tend to accumulate in the immune privileged core of solid tumors. The bacteria have been engineered to interact with tumor cells and deposit a synthetic antigen on the cells that can then be targeted by CAR T cells. The approach could enhance CAR T cell therapy in solid tumors, which hasn’t worked as well as CAR T cell therapy for blood-borne cancers to date. Creating such bacterial/T cell tag teams could expand the variety of cancers that can be treated using T cell therapy and also enhance the tumor cell killing effects of T cells.   

CAR T cells are white blood cells that have been primed to attack cancer cells. While this approach has worked reasonably well in blood-borne cancers, such as leukemia, it has proven more difficult to target solid tumors. Such solid tumors are dense, have an erratic blood supply, and the cells within the tumor contain many biochemical signals that are also found in healthy tissue, making it difficult to distinguish and target cancers. Using CAR T cells to targeting tumor antigens that naturally occur in such solid tumors does not typically appear to provide sufficient cell killing activity.

These issues prompted these Columbia researchers to design a little helper for CAR T cells that can paint the tumor cells with an irresistible synthetic antigen that the CAR T cells are highly disposed to target. “Our probiotic platform enables CAR-T cells to attack a broad range of tumor types,” said Tal Danino, a researcher involved in the study. “Traditional CAR-T therapies have relied on targeting natural tumor antigens. This is the first example of pairing engineered T cells with engineered bacteria to deliver synthetic antigens safely, systemically, and effectively to solid tumors. This could have a significant impact on the treatment of many cancers.”

Given that the bacteria naturally tend to accumulate at a tumor core, the system may represent a universal CAR-T technology, that can be used for any solid tumor, without the need to customize the system for each tumor type or patient. This could dramatically expand the types of tumors that can be treated in this way.

“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 Rosa Vincent, another researcher involved in the study. “We chose to bridge the individual limitations of these two cell therapies by combining the best features of each — using bacteria to place the targets, and T cells to destroy the malignant cells.”

Study in journal Science: Probiotic-guided CAR-T cells for solid tumor targeting

Via: Columbia University