{"doi":"10.1101/2023.08.28.555194","title":"L-DOS47 enhances response to immunotherapy in pancreatic cancer tumor","abstract":"Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds CEACAM6, a cell surface protein highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6. Our results demonstrate that combining L DOS47 with anti-PD1 significantly increases the efficacy of anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":410908,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":799781,"name":"Pietro Irrera","orcid":"0000-0002-3565-6523","position":1,"is_corresponding":false},{"id":257299,"name":"Dominique Abrahams","orcid":null,"position":2,"is_corresponding":false},{"id":256169,"name":"Verónica Estrella","orcid":"0000-0001-9943-544X","position":3,"is_corresponding":false},{"id":432808,"name":"Bryce Ordway","orcid":"0000-0002-1492-9473","position":4,"is_corresponding":false},{"id":400737,"name":"Samantha Byrne","orcid":null,"position":5,"is_corresponding":false},{"id":1191423,"name":"Andrew A. Ojeda","orcid":null,"position":6,"is_corresponding":false},{"id":3484,"name":"Christopher J. Whelan","orcid":"0000-0001-7511-2603","position":7,"is_corresponding":false},{"id":332433,"name":"Jongphil Kim","orcid":"0000-0002-7430-2226","position":8,"is_corresponding":false},{"id":256170,"name":"Matthew Beatty","orcid":"0000-0003-3198-9264","position":9,"is_corresponding":false},{"id":1191424,"name":"Sultan Damgaci-Erturk","orcid":null,"position":10,"is_corresponding":false},{"id":30125,"name":"Dario Livio Longo","orcid":"0000-0002-6906-9925","position":11,"is_corresponding":false},{"id":1191082,"name":"Kim Gaspar","orcid":"0009-0001-5934-5121","position":12,"is_corresponding":false},{"id":1191083,"name":"Gabrielle M. Siegers","orcid":"0000-0003-2154-0279","position":13,"is_corresponding":false},{"id":967125,"name":"Barbara A. Centeno","orcid":null,"position":14,"is_corresponding":false},{"id":1109234,"name":"Justin Y. C. Lau","orcid":"0000-0001-7316-811X","position":15,"is_corresponding":false},{"id":1138633,"name":"Arig Ibrahim-Hashim","orcid":null,"position":16,"is_corresponding":false},{"id":242938,"name":"Shari Pilon‐Thomas","orcid":"0000-0001-7785-3034","position":17,"is_corresponding":false},{"id":65782,"name":"Robert J. Gillies","orcid":"0000-0002-8888-7747","position":18,"is_corresponding":false},{"id":576282,"name":"Bruna V. Jardim‐Perassi","orcid":"0000-0001-5908-4470","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:21:38.940853Z","pmid":"37693389","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":[]}