{"doi":"10.1101/2024.07.16.603785","title":"Engineered NKG2C <sup>+</sup> NK-like T cells exhibit superior antitumor efficacy while mitigating cytokine release syndrome","abstract":"Abstract Engineered T and NK cell therapies have widely been used to treat hematologic malignancies and solid tumors, with promising clinical results. Current chimeric antigen receptor (CAR) T cell therapeutics have, however, been associated with treatment-related adverse events such as cytokine release syndrome (CRS) and are prone to immunologic exhaustion. CAR-NK therapeutics, while not associated with CRS, have limited in vivo persistence. We now demonstrate that an NK-like TCRαβ + CD8 T cell subset, identified and expanded ex vivo through its expression of the activating receptor NKG2C (NKG2C + NK-like T cells), can be transduced to express a second-generation CD19 CAR (1928z), resulting in superior tumor clearance, longer persistence and decreased exhaustion compared to conventional 1928z CAR + CD8 T cells and 1928z CAR+ NK cells. Moreover, CAR-modified NKG2C + NK-like T cells resulted in significantly reduced CRS compared to conventional CAR + CD8 T cells. Similarly, NKG2C + NK-like T cells engineered with a TCR targeting the NY-ESO-1 antigen exhibit robust tumor control and minimal exhaustion compared to TCR-engineered conventional CD8 T cells. These data establish NKG2C + NK-like T cells as a robust platform for cell engineering, and offer a safer, more durable alternative to conventional CAR-T and CAR-NK therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488748,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"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":749867,"name":"M. Kazim Panjwani","orcid":"0000-0002-2305-1164","position":1,"is_corresponding":false},{"id":1222645,"name":"Sanam Shahid","orcid":"0000-0003-4281-4910","position":2,"is_corresponding":false},{"id":749866,"name":"Rosa Sottile","orcid":"0000-0003-2950-9508","position":3,"is_corresponding":false},{"id":1333700,"name":"Clara Lawry","orcid":null,"position":4,"is_corresponding":false},{"id":1333701,"name":"Gabryelle Kolk","orcid":null,"position":5,"is_corresponding":false},{"id":1333702,"name":"Theodota Kontopolous","orcid":null,"position":6,"is_corresponding":false},{"id":268587,"name":"Anthony F. Daniyan","orcid":"0009-0002-2742-2281","position":7,"is_corresponding":false},{"id":488147,"name":"Smita S. Chandran","orcid":"0000-0001-9266-6878","position":8,"is_corresponding":false},{"id":311733,"name":"Christopher A. Klebanoff","orcid":"0000-0001-9645-3896","position":9,"is_corresponding":false},{"id":320883,"name":"Katharine C. Hsu","orcid":"0000-0003-2827-5324","position":10,"is_corresponding":false},{"id":684553,"name":"Kyle B. Lupo","orcid":"0000-0003-3442-0647","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:08:19.655720Z","pmid":"39211122","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":[]}