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.

Interferon-omega: Current status in clinical applications

“…Currently, few successful treatments for fibrosarcoma have been reported in cats, although treatment of feline fibrosarcoma with rFeIFN-ω has been demonstrated to be safe, well tolerated, and easily performed. A study by Hampel et al [103] revealed that rFeIFN-ω increased the expression of major histocompatibility I molecules on feline fibrosarcoma cells, while eosinophilia, neutropenia, and weight loss were remarkably reduced by rFeIFN-ω treatment. However, a placebo-controlled trial is needed.…”

Sarcomas—A barren immunological wasteland or field of opportunity for immunotherapy?

“…The overall goal of these approaches is to induce and/or augment tumour specific immune responses and counteract suppressive cell subsets within the TME to create a permissive milieu for effective anti‐tumour immunity. Key approaches to achieve this include: activation of non‐specific innate immunity, 74,75,91‐107 administration of tumour vaccines and cytokines, 108‐113 monoclonal antibodies (mAbs) to target uniquely expressed or over‐expressed cell surface antigens and promote antibody dependent cell mediated cytotoxicity (ADCC) or block checkpoint molecules unleashing anti‐tumour immunity, 114 adoptive transfer of polyclonal or genetically modified T cells, and modulation of the TME to minimize immunosuppression 63,115 …”

Sarcoma De Sítio De Aplicação Em Felinos

“…A ressecção cirúrgica do tumor deve alcançar 3-5 cm de margens laterais e duas camadas musculares ou osso como margem profunda (SCHERK et al, 2013;LADLOW, 2013 A imunoterapia adicional parece ter resultados promissores (HARTMANN et al, 2015). Um estudo utilizou interferon-ω felino para o tratamento de fibrossarcoma para avaliar sua segurança e viabilidade como uma opção de tratamento para gatos; foi considerado seguro e bem tolerado, porém ainda deve ser testado em um ensaio controlado com placebo para avaliar a eficácia no tratamento (HAMPEL et al, 2007). Kirpensteijn (2006) também cita que a utilização de gene da interleucina-2 pode promover menor recorrência do tumor associando à radioterapia e cirurgia.…”