{"doi":"10.1016/j.canlet.2024.217404","title":"A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models","abstract":"L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity. EBD-200 showed comparable anti-cancer effects to PEGylated L-ASNase in ASNS low ALL, melanoma and liver cancer models, with improved tolerability. Its potent anti-cancer efficacy and enhanced safety profile suggest that EBD-200 could benefit ALL patients and broaden treatment options for ASNS low solid cancers. • Similar durable in vivo anti-leukemic effect is seen with EBD-200 and PEG-ASNase. • Lower toxicity of EBD-200 versus PEG-ASNase correlates with lack of GLNase activity. • EBD-200 effectively treats ASNS low solid cancers with hypermethylated ASNS promoter.","journal":"Cancer Letters","year":2024,"id":455074,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":911703,"name":"Amanda M. Schalk","orcid":null,"position":1,"is_corresponding":false},{"id":1279357,"name":"Kenneth Hofkens","orcid":null,"position":2,"is_corresponding":false},{"id":910993,"name":"Evelien Peeters","orcid":"0000-0001-9438-1876","position":3,"is_corresponding":false},{"id":1278909,"name":"Sara T’Sas","orcid":"0000-0003-4256-9775","position":4,"is_corresponding":false},{"id":910992,"name":"Katrien Vandemeulebroecke","orcid":"0000-0002-0220-6892","position":5,"is_corresponding":false},{"id":910994,"name":"Ying Su","orcid":"0000-0001-8322-0655","position":6,"is_corresponding":false},{"id":1279358,"name":"Ashley De Loera","orcid":null,"position":7,"is_corresponding":false},{"id":1278910,"name":"A. García","orcid":"0000-0001-8388-0522","position":8,"is_corresponding":false},{"id":374127,"name":"Hui Chen","orcid":"0000-0002-7990-9254","position":9,"is_corresponding":false},{"id":525356,"name":"Tim Lammens","orcid":"0000-0001-8733-4027","position":10,"is_corresponding":false},{"id":241453,"name":"Pieter Van Vlierberghe","orcid":"0000-0001-9063-7205","position":11,"is_corresponding":false},{"id":678530,"name":"Steven Goossens","orcid":"0000-0002-5693-8570","position":12,"is_corresponding":false},{"id":488720,"name":"Arnon Lavie","orcid":"0000-0001-5591-8722","position":13,"is_corresponding":false},{"id":910989,"name":"Maaike Van Trimpont","orcid":"0000-0001-7033-9569","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"39709177","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":[]}