Cancer therapy with chimeric antigen receptor (CAR)-T cells has achieved impressive remissions in certain hematologic malignancies, and extending the approach to other types of cancer is a key goal of immunotherapy research. Solid tumors have proved particularly challenging because of immunosuppressive mechanisms in the tumor microenvironment. Writing in Science, Danino and colleagues outline a new strategy for deploying CAR-T cells against solid tumors: use engineered bacteria to coat the interior of the tumor with a synthetic antigen and then treat with CAR-T cells specific for the synthetic antigen.
Previous work has shown that engineered bacteria injected intratumorally or intravenously can colonize the hypoxic, necrotic core of a tumor and deliver various antitumor agents. In 2020, the Danino group reported an engineered Escherichia coli strain Nissle 1917 that released drugs selectively in tumors via a chromosomally integrated synchronized lysis circuit regulated by a quorum-sensing promoter. In their new paper, they adapt this system to tag tumors with a synthetic CAR antigen. The tag is a fusion of a heparin-binding protein, which binds the extracellular matrix of tumor stroma, and GFP, which serves as the antigen. The authors test their ‘probiotic-guided CAR-T cells’ (ProCARs) in mouse models of leukemia, colorectal cancer and breast cancer and find that sequential intratumoral injections of the bacteria and CAR-T cells are effective in reducing tumor volumes. In a variation of the approach, bacteria are engineered to deliver both the antigen tag and a chemokine that recruits T cells. Further research is needed to understand the potential of ProCARs for human cancer therapy.
This is a preview of subscription content, access via your institution