{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hu W"],"funding":["Scholarship of Pujiang Talents in Shanghai","National Natural Science Foundation of China"],"pagination":["365-377"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11028344"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["68(3)"],"pubmed_abstract":["The interaction between programmed cell death protein 1 (PD-1) on activated T cells and its ligands on a target tumour may limit the capacity of chimeric antigen receptor (CAR) T cells to eradicate solid tumours. PD-1 blockade could potentially enhance CAR T cell function. Here, we show that mesothelin is overexpressed in human triple-negative breast cancer cells and can be targeted by CAR T cells. To overcome the suppressive effect of PD-1 on CAR T cells, we utilized CRISPR/Cas9 ribonucleoprotein-mediated editing to disrupt the programmed cell death-1 (PD-1) gene locus in human primary T cells, resulting in a significantly reduced PD-1<sup>hi</sup> population. This reduction had little effect on CAR T cell proliferation but strongly augmented CAR T cell cytokine production and cytotoxicit"],"journal":["Cancer immunology, immunotherapy : CII"],"pubmed_title":["CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions."],"pmcid":["PMC11028344"],"funding_grant_id":["14PJ1405600","81402542"],"pubmed_authors":["Li G","Cai Q","Zi Z","Hu W","Shao K","Ma X","Wei F","Jin Y"],"additional_accession":[]},"is_claimable":false,"name":"CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions.","description":"The interaction between programmed cell death protein 1 (PD-1) on activated T cells and its ligands on a target tumour may limit the capacity of chimeric antigen receptor (CAR) T cells to eradicate solid tumours. PD-1 blockade could potentially enhance CAR T cell function. Here, we show that mesothelin is overexpressed in human triple-negative breast cancer cells and can be targeted by CAR T cells. To overcome the suppressive effect of PD-1 on CAR T cells, we utilized CRISPR/Cas9 ribonucleoprotein-mediated editing to disrupt the programmed cell death-1 (PD-1) gene locus in human primary T cells, resulting in a significantly reduced PD-1<sup>hi</sup> population. This reduction had little effect on CAR T cell proliferation but strongly augmented CAR T cell cytokine production and cytotoxicit","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2025-04-22T16:45:04.843Z","creation":"2025-04-06T01:50:16.302Z"},"accession":"S-EPMC11028344","cross_references":{"pubmed":["30523370"],"doi":["10.1007/s00262-018-2281-2"]}}