Current and Future Perspectives of CAR T-Cell Therapy in Pancreatic Cancer

Abstract

One of the deadliest cancers in the world is pancreatic cancer with contributing factors resulting from late diagnosis, rapid disease progression, and limited effective therapies. Fortunately, in recent years, immunotherapies like chimeric antigen receptors (CAR T-cells) have become very effective and successful in the treatment of hematologic cancers. With these favorable results, researchers are focusing on using CAR T-cells for solid cancers. This review examines some of the recent pre-clinical and clinical studies conducted over the past few years on promising targeted antigens for CAR T-Cells in pancreatic cancer, including but not limited to mesothelin, Claudin18.2, CD318, and PSCA. While these antigen CAR T-Cells showed positive results, multiple limitations reduce the effectiveness of the treatment. These major barriers include suppressive tumor microenvironment (TME), antigen loss and heterogeneity, or toxicity. Nonetheless, researchers continue to investigate new target antigens and strategies that could overcome these barriers and enhance the therapy’s safety and outcome like novel CAR designs.