Research progress and design optimization of CAR-T therapy for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR-T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR-T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR-T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the on-target, off-tumor effect. Applying neoantigens of PDAC as targets for CAR-T therapy, recognizing the CAR-T subgroup with better antitumor effect, and designing a CAR-T system targeting stroma of PDAC may contribute to develop a powerful CAR-T therapy for PDAC in the future.