{"doi":"10.1101/2020.01.17.909895","title":"Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting","abstract":"Abstract Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. To expand the targeting capabilities of these receptors, we have developed switchable adaptor receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody. Instead of directly targeting an antigen, our receptors contain the SNAPtag self-labeling enzyme, which reacts with benzylguanine (BG)-conjugated antibodies to assemble covalently-associated antigen receptors. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors and their downstream effector functions can be successfully targeted by several clinically-relevant BG-conjugated antibodies in an antigen-specific and antibody dose-dependent manner. To better define parameters affecting receptor signaling, we developed a mathematical model of switchable receptor systems. SNAP receptors provide a powerful new strategy to post-translationally reprogram the targeting specificity of engineered cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120840,"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":8,"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":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559132,"name":"Adam Butchy","orcid":"0000-0002-0096-0031","position":1,"is_corresponding":false},{"id":559133,"name":"Yaniv Tivon","orcid":"0000-0002-1573-4096","position":2,"is_corresponding":false},{"id":559134,"name":"Michael Kvorjak","orcid":"0000-0001-9195-8174","position":3,"is_corresponding":false},{"id":559135,"name":"Nataša Miškov-Živanov","orcid":"0000-0003-1110-3403","position":4,"is_corresponding":false},{"id":264203,"name":"Alexander Deiters","orcid":"0000-0003-0234-9209","position":5,"is_corresponding":false},{"id":402848,"name":"Olivera J. Finn","orcid":"0000-0003-0930-920X","position":6,"is_corresponding":false},{"id":559131,"name":"Jason Lohmueller","orcid":"0000-0001-6089-9992","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","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":[]}