{"doi":"10.1101/2023.09.13.557232","title":"Leucine zipper-based sorting system enables generation of multi-functional CAR T cells","abstract":"Abstract Resistance to chimeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms including antigen-loss escape and tumor-induced immune suppression. Expression of multiple CARs may overcome multi-antigen-loss escape. Similarly, expression of switch receptors that convert inhibitory immune checkpoint signals into positive costimulatory signals may enhance CAR T cell activity in the tumor microenvironment. Engineering multiple features into one cell product, however, is limited by transgene packaging constraints of current vector systems. Here, we describe a leucine zipper-based cell sorting methodology that enables selective single-step immunomagnetic purification of cells co-transduced with two vectors, designed to potentially double the number of incorporated transgenes. This “Zip-sorting” system facilitated generation of T cells simultaneously expressing up to four CARs and co-expressing up to three switch receptors. These multi-CAR multi-Switch receptor arrays enabled T cells to eliminate antigenically heterogeneous syngeneic leukemia populations co-expressing multiple inhibitory ligands. Zip-sorted multi-CAR multi-Switch receptor T cells represent a potent therapeutic strategy to overcome multiple mechanisms of CAR T cell resistance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400762,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"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":1177190,"name":"Sophia Chen","orcid":"0000-0001-6059-0661","position":1,"is_corresponding":false},{"id":1177191,"name":"Brandon D. Ng","orcid":"0009-0002-8614-9457","position":2,"is_corresponding":false},{"id":1177192,"name":"Jacob S. Fischman","orcid":"0000-0001-6907-5033","position":3,"is_corresponding":false},{"id":841671,"name":"Lorenz Jahn","orcid":"0000-0002-9880-7026","position":4,"is_corresponding":false},{"id":282396,"name":"Alexander P. Boardman","orcid":"0000-0001-7169-9275","position":5,"is_corresponding":false},{"id":336003,"name":"Adhithi Rajagopalan","orcid":"0000-0002-9251-0416","position":6,"is_corresponding":false},{"id":465768,"name":"Harold K. Elias","orcid":"0000-0002-6189-4752","position":7,"is_corresponding":false},{"id":1177193,"name":"Alyssa Massa","orcid":"0000-0001-7514-3573","position":8,"is_corresponding":false},{"id":1177194,"name":"Dylan Manuele","orcid":"0000-0002-7054-6709","position":9,"is_corresponding":false},{"id":345074,"name":"Katherine Nichols","orcid":"0000-0003-0817-1667","position":10,"is_corresponding":false},{"id":345067,"name":"Amina Lazrak","orcid":"0000-0001-8167-7803","position":11,"is_corresponding":false},{"id":661691,"name":"Nicole Lee","orcid":"0000-0001-6953-2177","position":12,"is_corresponding":false},{"id":457319,"name":"Teng Fei","orcid":"0000-0001-7888-1715","position":13,"is_corresponding":false},{"id":268582,"name":"Susan DeWolf","orcid":"0000-0002-2754-3537","position":14,"is_corresponding":false},{"id":225648,"name":"Jonathan U. Peled","orcid":"0000-0002-4029-7625","position":15,"is_corresponding":false},{"id":78951,"name":"Santosha A. Vardhana","orcid":"0000-0002-3100-1298","position":16,"is_corresponding":false},{"id":311733,"name":"Christopher A. Klebanoff","orcid":"0000-0001-9645-3896","position":17,"is_corresponding":false},{"id":108880,"name":"Marcel R.M. van den Brink","orcid":"0000-0003-0696-4401","position":18,"is_corresponding":false},{"id":702428,"name":"Scott E. James","orcid":"0000-0002-3601-6819","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","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":[]}