Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.
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.
Hüttinger
Cornelia
C
Clinic of Small Animal Medicine, Ludwig Maximilians University, Munich, Germany. C.Huettinger@medizinische-kleintierklinik.de
Hirschberger
Johannes
J
Jahnke
Anika
A
Köstlin
Roberto
R
Brill
Thomas
T
Plank
Christian
C
Küchenhoff
Helmut
H
Krieger
Stefan
S
Schillinger
Ulrike
U
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
D016178:Granulocyte-Macrophage Colony-Stimulating Factor