Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors

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dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.authorKing, Jamie N.en
dc.contributor.authorRobertson, John L.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorElankumaran, Subbiahen
dc.date.accessioned2024-02-13T20:03:48Zen
dc.date.available2024-02-13T20:03:48Zen
dc.date.issued2024-01-29en
dc.date.updated2024-02-09T15:06:27Zen
dc.description.abstractNeurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood&ndash;brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment. Dose-limiting toxicities manifested as fever, hematologic, and neurological adverse events, and the maximum tolerated dose (MTD) of rLAS-uPA was 2 &times; 10<sup>7</sup> pfu/mL. Mild adverse events, including transient infusion reactions, diarrhea, and fever were observed in 16/18 of dogs treated at or below MTD. No infectious virus was recoverable from body fluids. Neutralizing antibodies to rLAS-uPA were present in all dogs by 2 weeks post-treatment, and viral genetic material was detected in post-treatment tumors from six dogs. Tumor volumetric reductions occurred in 2/11 dogs receiving the MTD. Systemically administered rLAS-uPA NDV was safe and induced anti-tumor effects in canine brain tumors, although modifications to evade host anti-viral immunity are needed to optimize this novel therapy.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRossmeisl, J.H.; King, J.N.; Robertson, J.L.; Weger-Lucarelli, J.; Elankumaran, S. Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors. Cancers 2024, 16, 564.en
dc.identifier.doihttps://doi.org/10.3390/cancers16030564en
dc.identifier.urihttps://hdl.handle.net/10919/117995en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectdogen
dc.subjectbrainen
dc.subjectcentral nervous systemen
dc.subjectgliomaen
dc.subjectmeningiomaen
dc.subjectparamyxovirusen
dc.subjectviroimmunotherapyen
dc.titlePhase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumorsen
dc.title.serialCancersen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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