{"doi":"10.1101/2023.08.02.551530","title":"TRAFfic signals: High-throughput CAR discovery in NK cells reveals novel TRAF-binding endodomains that drive enhanced persistence and cytotoxicity","abstract":"Abstract Natural killer (NK) cells are a promising alternative therapeutic platform to CAR T cells given their favorable safety profile and potent killing ability. However, CAR NK cells suffer from limited persistence in vivo , which is, in part, thought to be the consequence of limited cytokine signaling. To address this challenge, we developed an innovative high-throughput screening strategy to identify CAR endodomains that could drive enhanced persistence while maintaining potent cytotoxicity. We uncovered a family of TRAF-binding endodomains that outperform benchmarks in primary NK cells along dimensions of persistence and cytotoxicity, even in low IL-2 conditions. This work highlights the importance of cell-type-specific cell therapy engineering and unlocks a wide range of high-throughput molecular engineering avenues in NK cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393510,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":603030,"name":"Aye T. Chen","orcid":null,"position":1,"is_corresponding":false},{"id":27300,"name":"Matthew R. Stone","orcid":"0000-0002-6575-7253","position":2,"is_corresponding":false},{"id":1167575,"name":"Lan Guo","orcid":"0000-0001-7097-4749","position":3,"is_corresponding":false},{"id":1167576,"name":"Brian J. Belmont","orcid":"0000-0002-8314-4565","position":4,"is_corresponding":false},{"id":1168051,"name":"Rebekah Turk","orcid":null,"position":5,"is_corresponding":false},{"id":1168052,"name":"Nick Bogard","orcid":null,"position":6,"is_corresponding":false},{"id":1162103,"name":"Nora Kearns","orcid":null,"position":7,"is_corresponding":false},{"id":1167577,"name":"Mary H. Young","orcid":"0000-0003-2921-6107","position":8,"is_corresponding":false},{"id":1168053,"name":"Bryce Daines","orcid":null,"position":9,"is_corresponding":false},{"id":841338,"name":"Max Darnell","orcid":"0000-0003-2411-5403","position":10,"is_corresponding":false},{"id":1168050,"name":"Maddie D. Williams","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37577560","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":[]}