Phase I Clinical Trial of Recombinant Oncolytic Newcastle Disease Virus for Intracranial Meningioma

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dc.contributor.authorKing, Jamie N.en
dc.contributor.committeechairRossmeisl, John H. Jr.en
dc.contributor.committeememberClapp, Kembaen
dc.contributor.committeememberLahmers, Kevin K.en
dc.contributor.departmentVeterinary Medicineen
dc.date.accessioned2019-01-06T07:01:09Zen
dc.date.available2019-01-06T07:01:09Zen
dc.date.issued2017-07-14en
dc.description.abstractMeningioma is one of the most commonly diagnosed intracranial tumors in dogs and humans. Treatment failures resulting in local recurrence and death remain common in tumors of high grade, prompting a need for additional therapeutic options that are both effective and affordable. Genetic modification of the LaSota strain of Newcastle Disease Virus (rLAS) has allowed the virus' fusion protein cleavage site to be replaced with that belonging to urokinase plasminogen activator (rLAS-uPA). This site is cleavable exclusively by the uPA receptor (uPAR), which is overexpressed in canine meningioma. The rLAS-uPA represents a targeted therapy that has the potential to be efficacious against meningioma when administered systemically. A Phase I clinical trial was designed to evaluate the safety and preliminary efficacy of rLAS-uPA administered to dogs with presumptive intracranial meningioma. The primary endpoint was to define the safety of rLAS-uPA, as determined by serial clinical and laboratory assessments during and after viral administration, using standard toxicity metrics defined by the Veterinary Cooperative Oncology Group (VCOG). Secondary end-points included anti-tumor activity quantified by magnetic resonance imaging (MRI) assessment of tumor size, and characterization of immune responses to the rLAS-uPA. Four dogs completed the trial without significant toxicity. No objective tumor responses were noted on MRI from any dog. All dogs produced antiviral antibodies and increased circulating cytokines during the course of treatment. No virus was recovered from plasma, urine, or cerebrospinal fluid. These results indicate that further investigation into the rLAS-uPA dose intensity and interval are required to further develop this therapy.en
dc.description.abstractgeneralThe use of a modified Newcastle Disease Virus intravenous infusion to treat brain tumors in dogs has been shown to have no overt significant adverse effects. However, further investigation is required to determine the efficacy and optimal dosing protocol for this potential treatment.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:12488en
dc.identifier.urihttp://hdl.handle.net/10919/86617en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectMeningiomaen
dc.subjectNewcastle Disease Virusen
dc.subjectCanineen
dc.subjectOncolytic Therapyen
dc.titlePhase I Clinical Trial of Recombinant Oncolytic Newcastle Disease Virus for Intracranial Meningiomaen
dc.typeThesisen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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