Jin C, Ma J, Ramachandran M, et al. CAR T Cells Expressing a Bacterial Virulence Factor Trigger Potent Bystander Antitumor Responses in Solid Cancers. Nature Biomedical Engineering. 2022; (doi: 10.1038/s41551-022-00875-5).
Mouse studies indicate that bolstering chimeric antigen receptor T cells (CAR T) with neutrophil-activating protein (NAP) from Helicobacter pylori could increase their efficacy against solid tumors. Unlike hematologic malignancies that respond favorably to the therapy, an immunosuppressive microenvironment and heterogeneous expression of tumor-associated antigens dilute the effect of CAR T in solid tumors. However, researchers found that mice with certain carcinomas and neuroblastomas registered slower tumor progression and improved survival rates with CAR(NAP) T cells than seen with traditional murine CAR T cells. In solid tumors with heterogeneous antigen expression, NAP secretion promotes a microenvironment that stimulates dendritic cell maturation and bystander T-cell response. As part of that response, endogenous CD8+ T cells targeting tumor-associated antigens other than the one targeted by CAR are activated — a key pathway for eradicating antigen-heterogenous solid tumors. Importantly, the investigators note, arming CAR T cells with NAP, a bacteria-derived virulence factor, does not appear to increase off-tumor toxicity or blunt the cytotoxic effect of CAR T cells.