Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.
Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.
Jahnke
A
A
Clinic of Small Animal Medicine, Ludwig Maximilian University Munich, Veterinärstr. 13, 80539 Munich, Germany. anika.jahnke@gmx.de
Hirschberger
J
J
Fischer
C
C
Brill
T
T
Köstlin
R
R
Plank
C
C
Küchenhoff
H
H
Krieger
S
S
Kamenica
K
K
Schillinger
U
U
D000818:Animals; D002371:Cat Diseases / Q000628:therapy*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000628:therapy / Q000662:veterinary*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods / Q000662:veterinary*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D008280:Magnetics; D008297:Male; D011994:Recombinant Proteins; D012449:Safety; D016896:Treatment Outcome
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor