{"doi":"10.1101/2021.07.09.450900","title":"CARPOOL: A library-based platform to rapidly identify next generation chimeric antigen receptors","abstract":"Abstract CD19-targeted CAR therapies have successfully treated B cell leukemias and lymphomas, but many responders later relapse or experience toxicities. CAR intracellular domains (ICDs) are key to converting antigen recognition into anti-tumor effector functions. Despite the many possible immune signaling domain combinations that could be included in CARs, almost all CARs currently rely upon CD3 ζ , CD28, and/or 4-1BB signaling. To explore the signaling potential of CAR ICDs, we generated a library of 700,000 CD19 CAR molecules with diverse signaling domains and developed a high throughput screening platform to enable optimization of CAR signaling for anti-tumor functions. Our strategy identifies CARs with novel signaling domain combinations that elicit distinct T cell behaviors from a clinically available CAR, including enhanced proliferation and persistence, lower exhaustion, potent cytotoxicity in an in vitro tumor rechallenge condition, and comparable tumor control in vivo . This approach is readily adaptable to numerous disease models, cell types, and selection conditions, making it a promising tool for rapidly improving adoptive cell therapies and expanding their utility to new disease indications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216684,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":54223,"name":"Khloe S. Gordon","orcid":"0000-0003-3652-7245","position":1,"is_corresponding":false},{"id":812604,"name":"Caleb R. Perez","orcid":"0000-0001-8709-6145","position":2,"is_corresponding":false},{"id":560675,"name":"Patrick V. Holec","orcid":"0000-0003-2342-7616","position":3,"is_corresponding":false},{"id":35402,"name":"Azucena Ramos","orcid":null,"position":4,"is_corresponding":false},{"id":812605,"name":"Angela Q. Zhang","orcid":"0000-0003-2599-2774","position":5,"is_corresponding":false},{"id":812606,"name":"Yunpeng Liu","orcid":"0000-0002-0959-0209","position":6,"is_corresponding":false},{"id":54231,"name":"Catherine Koch","orcid":"0000-0003-0790-1429","position":7,"is_corresponding":false},{"id":333735,"name":"Alina Starchenko","orcid":"0000-0003-2265-7508","position":8,"is_corresponding":false},{"id":231599,"name":"Brian A. Joughin","orcid":"0000-0003-1022-9450","position":9,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":10,"is_corresponding":false},{"id":236278,"name":"Darrell J. Irvine","orcid":"0000-0002-8637-1405","position":11,"is_corresponding":false},{"id":35369,"name":"Michael T. Hemann","orcid":"0000-0001-6776-2163","position":12,"is_corresponding":false},{"id":17259,"name":"Michael E. Birnbaum","orcid":"0000-0002-2281-3518","position":13,"is_corresponding":false},{"id":54219,"name":"Taeyoon Kyung","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","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":[]}