Efficient Artificial T Cell Therapy for Bacterial-Colonized Tumors

Abstract

Tumor-colonizing bacteria can impede the efficacy of cancer treatments and elevate the risk of metastatic spread. While cytotoxic T lymphocytes (CTLs) are essential for destroying tumor cells, they lack the ability to eliminate bacteria. Here, the artificial T cells (ATC) are presented for tumors, particularly those colonized with intracellular bacteria. The ATC is composed of a hydrogel framework made of disulfide-linked chitosan and hyaluronic acid, encapsulating T cell-derived granzyme B and phage-derived holin. This design leverages the tumor microenvironment for the targeted release of these antitumor and antibacterial agents to precisely kill tumor cells and intracellular bacteria. In vivo studies demonstrate the debris from ATC-mediated destruction acts as an immune stimulator, promoting immune cell infiltration and inhibiting tumor migration. This work highlights the potential of ATC therapy in achieving targeted treatment and robust anti-tumor immunity, advancing the field of artificial cell technologies for precision medicine.