Adjuvant Immunotherapy of Feline Fibrosarcoma with Recombinant Feline Interferon-ω

Abstract

Background: Recombinant feline interferon-v (rFeIFN-v) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility.Hypothesis: Treatment with rFeIFN-v in cats with fibrosarcoma is safe and feasible. Animals: Twenty domestic cats. Methods:In an open-labeled uncontrolled clinical trial 12 injections of 1 3 10 6 U/kg rFeIFN-v were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-v. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-v and recombinant feline interferon-c was performed to assess the biological effect of rFeIFN-v.Results: Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P 5 .025), neutropenia (P 5 .021), and weight loss (P , .001) were statistically correlated with rFeIFN-v-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-v). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P 5 .026) in response to in vitro incubation with rFeIFN-v, whereas expression of MHC class II molecules was not affected significantly.Conclusions and Clinical Importance: RFeIFN-v for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.

Effect of recombinant feline interferon‐ω alone and in combination with chemotherapeutic agents on putative tumour‐initiating cells and daughter cells derived from canine and feline mammary tumours

“…In vivo, IFN can affect the differentiation and activity of host immune cells and exert anti‐angiogenic activity (indirect activity) 30 . rFeIFN‐ω was shown to increase the expression of major histocompatibility complex class I molecules on five unrelated feline fibrosarcoma cell lines 15 . Human preclinical studies on the antitumour efficacy of IFN‐ω rely on xenogeneic models of human cancer in immunodeficient mice because of the lack of IFN‐ω genes in mice 30,31 .…”

“…A recombinant feline IFN‐ω (rFeIFN‐ω, Virbagen Omega®, Virbac) has been approved for use in cats and dogs against selected infectious diseases 11,12 and has demonstrated in vitro growth inhibition activities on various canine and feline cell lines 13,14 . In a recent clinical study of feline fibrosarcoma, rFeIFN‐ω was shown to be safe and well tolerated for the treatment of this disease but few conclusions could be drawn on its antineoplastic activity because of the lack of clinical controls 15 …”

Immunotherapy in Veterinary Oncology

“…Many have investigated the in vitro and/or in vivo effects of the soluble cytokine (eg, interferons, IL-2, IL-12, and IL-15) [38][39][40][41][42][43][44][45][46][47][48][49] or liposome encapsulation of the cytokine (eg, liposomal IL-2) 39,50-53 or use a virus, cell, liposome-DNA complex, plasmid, or other mechanism to expresses the cytokine (eg, recombinant poxvirus expressing IL-2). 50,54-61 The European Committee for Medicinal Products for Veterinary Use adopted a positive opinion in March 2013 for the veterinary product, Oncept IL-2 (feline poxvirus expressing recombinant feline IL-2).…”

Musculoskeletal neoplasia

“…45 Feline interferonomega injected intratumourally and at the tumour excision site has been shown to be safe, 46 but there are no studies regarding its efficacy. Although mainly a spontaneous tumour, OSA has also been described secondary to forelimb fracture 55,56 and radiotherapy.…”