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Neoadjuvant gene delivery of feline granulocyte‐macrophage colony‐stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial
Author(s) -
Hüttinger Cornelia,
Hirschberger Johannes,
Jahnke Anika,
Köstlin Roberto,
Brill Thomas,
Plank Christian,
Küchenhoff Helmut,
Krieger Stefan,
Schillinger Ulrike
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1185
Subject(s) - cats , toxicity , medicine , granulocyte macrophage colony stimulating factor , adverse effect , genetic enhancement , gastroenterology , pharmacology , oncology , gene , biology , cytokine , biochemistry
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 µg. 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 µg of feGM‐CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing. Copyright © 2008 John Wiley & Sons, Ltd.