{"doi":"10.1016/j.celrep.2024.114867","title":"Developing enhanced immunotherapy using NKG2A knockout human pluripotent stem cell-derived NK cells","abstract":"Cancer immunotherapy is gaining increasing attention. However, immune checkpoints are exploited by cancer cells to evade anti-tumor immunotherapy. Here, we knocked out NKG2A, an immune checkpoint expressed on natural killer (NK) cells, in human pluripotent stem cells (hPSCs) and differentiated these hPSCs into NK (PSC-NK) cells. We show that NKG2A knockout (KO) enhances the anti-tumor and anti-viral capabilities of PSC-NK cells. NKG2A KO endows PSC-NK cells with higher cytotoxicity against HLA-E-expressing glioblastoma (GBM) cells, leukemia cells, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells in vitro. The NKG2A KO PSC-NK cells also exerted potent anti-tumor activity in vivo, leading to substantially suppressed tumor progression and prolonged survival of tumor-bearing mice in a xenograft GBM mouse model. These findings underscore the potential of PSC-NK cells with immune checkpoint KO as a promising cell-based immunotherapy. The unlimited supply and ease of genetic engineering of hPSCs makes genetically engineered PSC-NK an attractive option for easily accessible \"off-the-shelf\" cancer immunotherapy.","journal":"Cell Reports","year":2024,"id":426214,"datarank":0.7249797269826427,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.275619885949544,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.275619885949544,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":19,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE241039"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":486833,"name":"Qi Cui","orcid":"0009-0009-5054-5221","position":1,"is_corresponding":false},{"id":486834,"name":"Guihua Sun","orcid":"0000-0001-7337-3543","position":2,"is_corresponding":false},{"id":487671,"name":"Jianfei Chao","orcid":null,"position":3,"is_corresponding":false},{"id":1086858,"name":"Cheng Wang","orcid":"0000-0001-6075-2878","position":4,"is_corresponding":false},{"id":274823,"name":"Xianwei Chen","orcid":"0000-0002-4552-9851","position":5,"is_corresponding":false},{"id":391295,"name":"Peng Ye","orcid":"0000-0002-8327-2241","position":6,"is_corresponding":false},{"id":486835,"name":"Tao Zhou","orcid":"0000-0003-2219-6385","position":7,"is_corresponding":false},{"id":869247,"name":"Arjit Vijey Jeyachandran","orcid":null,"position":8,"is_corresponding":false},{"id":1123495,"name":"Olivia Sun","orcid":"0009-0009-4011-0750","position":9,"is_corresponding":false},{"id":980853,"name":"Wei Liu","orcid":"0000-0003-0004-2713","position":10,"is_corresponding":false},{"id":1225685,"name":"Shunyu Yao","orcid":null,"position":11,"is_corresponding":false},{"id":1129859,"name":"Chance Palmer","orcid":null,"position":12,"is_corresponding":false},{"id":379083,"name":"Xuxiang Liu","orcid":"0000-0002-1677-0814","position":13,"is_corresponding":false},{"id":232372,"name":"Vaithilingaraja Arumugaswami","orcid":"0000-0002-6872-5118","position":14,"is_corresponding":false},{"id":838694,"name":"Wing C. Chan","orcid":"0000-0002-1067-8216","position":15,"is_corresponding":false},{"id":289779,"name":"Xiuli Wang","orcid":"0000-0001-5964-4327","position":16,"is_corresponding":false},{"id":274829,"name":"Yanhong Shi","orcid":"0000-0002-3938-5839","position":17,"is_corresponding":false},{"id":486836,"name":"Yue Qin","orcid":"0000-0003-4277-3602","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:58:37.924718Z","pmid":"39447568","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}