{"doi":"10.1016/j.jamcollsurg.2019.12.027","title":"Novel Chimeric Immuno-Oncolytic Virus CF33-hNIS-antiPDL1 for the Treatment of Pancreatic Cancer","abstract":"BACKGROUND: Peritoneal carcinomatosis (PC) from pancreatic ductal adenocarcinoma (PDAC) is fatal. Our preclinical study presents an effective treatment against PDAC PC using a novel oncolytic viral agent, CF33-hNIS-antiPDL1. STUDY DESIGN: CF33-hNIS-antiPDL1 is a genetically engineered chimeric orthopoxvirus, CF33, armed with the human Sodium Iodide Symporter (hNIS) and anti-PD-L1 antibody (anti-PD-L1). The in vitro cytotoxic ability of this virus against 5 PDAC cell lines was tested at various doses (multiplicity of infection [MOI] = 0.01, 0.1, 1, 10). Production and blockade function of virus-encoded anti-PD-L1 antibody were verified using immunoblot, immunoprecipitation, and PD-1/PD-L1 bioassay. In vivo mouse models of PC, with or without subcutaneous (SC) tumors, created by injecting AsPC-1-ffluc cells into nude mice, were treated with PBS or a single dose (1×105 plaque-forming units) of either intraperitoneal (IP) or IV injection of CF33-hNIS-antiPDL1. Mice with PC tumors were treated on days 0, 2, or 14 after tumor implantation. RESULTS: CF33-hNIS-antiPDL1 killed PDAC cells in a dose-dependent manner, achieving >90% cell killing by day 8. Cells infected with CF33-hNIS-antiPDL1 produced bioactive anti-PD-L1 antibody, which blocked PD-1/PD-L1 interaction. In vivo, a single dose of virus reduced tumor burden and prolonged survival of treated mice. It was observed that IP administration of CF33-hNIS-antiPDL1 was more effective than IV administration. CONCLUSIONS: CF33-hNIS-antiPDL1 virus is effective in infecting and killing human PDACs and producing functional anti-PD-L1 antibody. Intraperitoneal delivery of CF33-hNIS-antiPDL1 effectively reduces peritoneal tumor burden and improves survival after only 1 dose and is superior to IV delivery.","journal":"Journal of the American College of Surgeons","year":2020,"id":63893,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"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":337771,"name":"Zhifang Zhang","orcid":"0000-0002-1047-2402","position":1,"is_corresponding":false},{"id":337772,"name":"Annie Yang","orcid":"0000-0001-6997-6130","position":2,"is_corresponding":false},{"id":337773,"name":"Shyambabu Chaurasiya","orcid":"0000-0002-9543-5458","position":3,"is_corresponding":false},{"id":337774,"name":"Anthony K. Park","orcid":"0000-0001-7692-8874","position":4,"is_corresponding":false},{"id":7770,"name":"Jianming Lü","orcid":"0000-0002-3794-641X","position":5,"is_corresponding":false},{"id":337775,"name":"Sang‐In Kim","orcid":"0000-0003-3961-6083","position":6,"is_corresponding":false},{"id":337776,"name":"Susanne G. Warner","orcid":"0000-0003-4329-7943","position":7,"is_corresponding":false},{"id":87998,"name":"Daniel D. Von Hoff","orcid":"0000-0003-4723-7681","position":8,"is_corresponding":false},{"id":337777,"name":"Yuman Fong","orcid":"0000-0002-8934-9959","position":9,"is_corresponding":false},{"id":337770,"name":"Yanghee Woo","orcid":"0000-0002-6676-0593","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-18T21:11:24.000992Z","pmid":"32032721","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":[]}