{"doi":"10.1101/2020.01.24.918888","title":"Chlorotoxin Redirects Chimeric Antigen Receptor T Cells for Specific and Effective Targeting of Glioblastoma","abstract":"Abstract While chimeric antigen receptor (CAR) T cells have demonstrated antitumor activity against glioblastoma (GBM), tumor heterogeneity remains a critical challenge. To more effectively target heterogeneous GBMs, we report the development of a novel peptide-based CAR exploiting the GBM-binding potential of chlorotoxin (CLTX). CLTX bound a greater proportion of tumor cells than GBM-associated antigens EGFR, HER2 and IL13Rα2. CAR T cells bearing CLTX as the targeting domain (CLTX-CAR), mediated potent in vitro and in vivo anti-GBM activity, and efficiently targeted tumors lacking expression of other GBM-associated antigens. Importantly, CLTX-CAR T cells exhibited no observable off-target effector activity against normal cells, or when adoptively transferred into mice. Effective targeting by CLTX-CAR T cells required cell surface expression of matrix metalloproteinase-2 (MMP-2). Our results are the first demonstration of a peptide toxin utilized as a CAR targeting domain, expanding the repertoire of tumor-selective CAR T cells with the potential to reduce antigen escape. One Sentence Summary Chimeric antigen receptors incorporating chlorotoxin as the tumor targeting domain recognize and kill glioblastoma with high specificity and potency.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124557,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":0.952,"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":249976,"name":"Renate Starr","orcid":"0000-0002-2200-6900","position":1,"is_corresponding":false},{"id":568600,"name":"Wen-Chung Chang","orcid":"0000-0002-1982-0725","position":2,"is_corresponding":false},{"id":249972,"name":"Brenda Aguilar","orcid":"0000-0002-6408-8422","position":3,"is_corresponding":false},{"id":249973,"name":"Darya Alizadeh","orcid":"0000-0003-1676-1181","position":4,"is_corresponding":false},{"id":569665,"name":"Sarah Wright","orcid":"0000-0002-9539-3796","position":5,"is_corresponding":false},{"id":274014,"name":"Xin Yang","orcid":"0000-0003-2744-7622","position":6,"is_corresponding":false},{"id":249977,"name":"Alfonso Brito","orcid":"0000-0001-7916-5745","position":7,"is_corresponding":false},{"id":458068,"name":"Aniee Sarkissian","orcid":null,"position":8,"is_corresponding":false},{"id":569666,"name":"Julie R. Ostberg","orcid":"0000-0001-5439-3725","position":9,"is_corresponding":false},{"id":274829,"name":"Yanhong Shi","orcid":"0000-0002-3938-5839","position":10,"is_corresponding":false},{"id":274021,"name":"Margarita Gutova","orcid":"0000-0002-7094-626X","position":11,"is_corresponding":false},{"id":388304,"name":"Karen S. Aboody","orcid":"0000-0002-1222-5114","position":12,"is_corresponding":false},{"id":249978,"name":"Behnam Badie","orcid":"0000-0001-9811-9306","position":13,"is_corresponding":false},{"id":249979,"name":"Stephen J. Forman","orcid":"0000-0002-2803-4152","position":14,"is_corresponding":false},{"id":274020,"name":"Michael E. Barish","orcid":"0000-0003-3011-4861","position":15,"is_corresponding":false},{"id":249980,"name":"Christine E. Brown","orcid":"0000-0003-4915-8207","position":16,"is_corresponding":false},{"id":249971,"name":"Dongrui Wang","orcid":"0000-0002-0859-7281","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:11.632153Z","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":[]}