{"doi":"10.17615/ystc-5b36","title":"Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β","abstract":"Cord blood (CB)-derived natural killer (NK) cells that are genetically engineered to express a chimeric antigen receptor (CAR) are an attractive off-the-shelf therapy for the treatment of cancer, demonstrating a robust safety profile in vivo. For poor prognosis brain tumors such as glioblastoma multiforme (GBM), novel therapies are urgently needed. Although CAR-T cells demonstrate efficacy in preclinical GBM models, an off-the-shelf product may exhibit unwanted side effects like graft-versus-host disease. Hence, we developed an off-the-shelf CAR-NK cell approach using a B7H3 CAR and showed that CAR-transduced NK cells have robust cytolytic activity against GBM cells in vitro. However, transforming growth factor (TGF)-β within the tumor microenvironment has devastating effects on the cytolytic activity of both unmodified and CAR-transduced NK cells. To overcome this potent immune suppression, we demonstrated that co-transducing NK cells with a B7H3 CAR and a TGF-β dominant negative receptor (DNR) preserves cytolytic function in the presence of exogenous TGF-β. This study demonstrates that a novel DNR and CAR co-expression strategy may be a promising therapeutic for recalcitrant CNS tumors like GBM.","journal":"UNC Libraries","year":2024,"id":499651,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"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":239814,"name":"Barbara Savoldo","orcid":"0000-0002-7571-3887","position":1,"is_corresponding":false},{"id":62902,"name":"Matthias Holdhoff","orcid":"0000-0002-3285-3484","position":2,"is_corresponding":false},{"id":1348412,"name":"Lazarski C.A","orcid":null,"position":3,"is_corresponding":false},{"id":500917,"name":"Ehsan Dowlati","orcid":"0000-0001-6739-0793","position":4,"is_corresponding":false},{"id":727516,"name":"Eric Yvon","orcid":"0000-0003-3822-6710","position":5,"is_corresponding":false},{"id":1348413,"name":"Bollard C.M","orcid":null,"position":6,"is_corresponding":false},{"id":1347588,"name":"A.J. Geiger","orcid":"0000-0002-2486-0553","position":7,"is_corresponding":false},{"id":1348414,"name":"Sohai D.K","orcid":null,"position":8,"is_corresponding":false},{"id":1348415,"name":"Cruz C.R.Y","orcid":null,"position":9,"is_corresponding":false},{"id":265275,"name":"Kajal Chaudhry","orcid":null,"position":10,"is_corresponding":false},{"id":227888,"name":"Robert S. Jones","orcid":"0000-0002-5283-8070","position":11,"is_corresponding":false},{"id":1348416,"name":"Hwang E.I","orcid":null,"position":12,"is_corresponding":false},{"id":1348411,"name":"H. Lang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:53.188165Z","pmid":null,"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":[]}