Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer
Ching‐Yao Yang, Ming Huei Fan, Carol H. Miao, Yi‐Jen Liao, Ray‐Hwang Yuan, Chao-Lien Liu
Abstract
. Adoptive transfer of both CAR T cells enhanced T cell persistence and induced specific regression of established CFPAC1 cancer by >80% in both xenograft and orthotopic models. Ki67 expression in tumors decreased, whereas proinflammatory cytokines/chemokines increased in CAR T cell-treated mouse sera. PD1ACR and PDL1CAR obtained a similar therapeutic efficacy. Thus, these armed third-generation PD-L1-targeted CAR T cells confer antitumor activity and the ability to combat T cell exhaustion, providing a potentially new and innovative CAR T cell immunotherapy against pancreatic cancers.
Topics & Concepts
CD137Chimeric antigen receptorCancer researchPancreatic cancerImmunotherapyTumor microenvironmentCD28Immune checkpointT cellImmune systemCancer immunotherapyAntigenAdoptive cell transferCancerProinflammatory cytokineBiologyImmunologyMedicineInternal medicineInflammationCAR-T cell therapy researchCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses