title: Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.
abstract: Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.
authors.affiliation: Clinic of Small Animal Medicine, Ludwig Maximilians University, Munich, Germany. C.Huettinger@medizinische-kleintierklinik.de
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hüttinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Hirschberger
authors.forename: Anika
authors.initials: A
authors.lastname: Jahnke
authors.forename: Roberto
authors.initials: R
authors.lastname: Köstlin
authors.forename: Thomas
authors.initials: T
authors.lastname: Brill
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Helmut
authors.initials: H
authors.lastname: Küchenhoff
authors.forename: Stefan
authors.initials: S
authors.lastname: Krieger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schillinger
mesh_terms: D000818:Animals; D002371:Cat Diseases / Q000276:immunology / Q000628:therapy*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D018014:Gene Transfer Techniques / Q000662:veterinary*; D015316:Genetic Therapy / Q000379:methods / Q000662:veterinary*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000378:metabolism*; D008280:Magnetics; D053758:Nanoparticles / Q000627:therapeutic use; D020360:Neoadjuvant Therapy / Q000379:methods / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor