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.
Clinic of Small Animal Medicine, Ludwig Maximilian University Munich, Veterinärstr. 13, 80539 Munich, Germany. anika.jahnke@gmx.de
A
A
Jahnke
J
J
Hirschberger
C
C
Fischer
T
T
Brill
R
R
Köstlin
C
C
Plank
H
H
Küchenhoff
S
S
Krieger
K
K
Kamenica
U
U
Schillinger
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