Adjuvant immunotherapy of feline injection-site sarcomas with the recombinant canarypox virus expressing feline interleukine-2 evaluated in a controlled monocentric clinical trial when used in association with surgery and brachytherapy

Jas, D.; Soyer, Canan; Fornel-Thibaud, P De; Oberli, Frantz; Vernes, D.; Guigal, Pierre-Michel; Poulet, Hervé; Devauchelle, Patrick

doi:10.1016/j.trivac.2014.11.001

Cited by 21 publications

(30 citation statements)

References 28 publications

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“…Other treatments that can be commercially obtained include feline interleukin-2, expressed by a recombinant canarypox virus, which functions as an immune stimulator. The effectiveness and the prognosis is generally better than regular surgical excision [38]. Even though comprehensive strategies for improvements in therapies have been widely investigated, FISS remains a therapeutic challenge.…”

Section: Discussionmentioning

confidence: 99%

Role of nuclear factor-kappa B in feline injection site sarcoma

Hsueh

Shih

et al. 2019

BMC Vet Res

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BackgroundChronic inflammation has been implicated in sarcomagenesis. Among various factors, activation of nuclear factor-kappa B (NF-κB) signaling pathway has been documented being able to target genes associated with tumor progression and up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. Feline injection sites sarcomas (FISS) are malignant entities derived from the mesenchymal origin. The disease has been considered to be associated with vaccine adjuvant, aluminum, which serves as a stimulus continuously inducing overzealous inflammatory and immunologic reactions. To understand the contribution of NF-κB in FISS, detection of activated NF-κB in paraffin-embedded specimens, in vitro establishment of primary cells derived from FISS, and evaluation of the effects of the NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on primary tumor cells were conducted.ResultsIn this study, nuclear expression of NF-κB p65 was detected in 83.3% of FISS cases and not correlated with tumor grading, sex, and age. Primary cells derived from FISS in three cats exhibiting same immunohistochemical characteristics as their original tumor were successfully established. The NF-κB inhibitor, DHMEQ, was able to prevent nuclear translocation of NF-κB p65, inhibit cell proliferation, migration, and colonization in dosage-dependent manners, and induce cell apoptosis in these primary FISS cells.ConclusionsHigh expression rate of nuclear NF-κB p65 in FISS cases and dose-dependent inhibitory effects on the growth of FISS primary cells treated with NF-κB inhibitor suggested that NF-κB might be a potential molecular therapeutic target for FISS.

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Section: Discussionmentioning

confidence: 99%

Role of nuclear factor-kappa B in feline injection site sarcoma

Hsueh

Shih

et al. 2019

BMC Vet Res

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“…IL-2 has antitumor activity and, in humans, recombinant IL-2 immunotherapy has been used clinically for treating melanoma. In the context of feline fibrosarcoma, adjuvant immunotherapy with local injection of recombinant human IL-2 extended survival times [63] and local canarypox-vectored recombinant IL-2 immunotherapy significantly reduced recurrence rates in cat fibrosarcomas [64, 65]. Genes annotated as having functions related to the regulation of production of the cytokine interleukin-12 (IL-12) (e.g., ACP5, CCR7, MAST2, IDO1, RIPK2, TLR4, IL10, MEFV, TLR2, IRF8, NFKB1, IFNG, JAK3, TIRAP, IL12B) were enriched among genes upregulated in FISS at FDR < 0.02 with a GSEA enrichment score of 2.2.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach

et al. 2019

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Background Feline injection-site sarcoma (FISS), an aggressive iatrogenic subcutaneous malignancy, is challenging to manage clinically and little is known about the molecular basis of its pathogenesis. Tumor transcriptome profiling has proved valuable for gaining insights into the molecular basis of cancers and for identifying new therapeutic targets. Here, we report the first study of the FISS transcriptome and the first cross-species comparison of the FISS transcriptome with those of anatomically similar soft-tissue sarcomas in dogs and humans. Methods Using high-throughput short-read paired-end sequencing, we comparatively profiled FISS tumors vs. normal tissue samples as well as cultured FISS-derived cell lines vs. skin-derived fibroblasts. We analyzed the mRNA-seq data to compare cancer/normal gene expression level, identify biological processes and molecular pathways that are associated with the pathogenesis of FISS, and identify multimegabase genomic regions of potential somatic copy number alteration (SCNA) in FISS. We additionally conducted cross-species analyses to compare the transcriptome of FISS to those of soft-tissue sarcomas in dogs and humans, at the level of cancer/normal gene expression ratios. Results We found: (1) substantial differential expression biases in feline orthologs of human oncogenes and tumor suppressor genes suggesting conserved functions in FISS; (2) a genomic region with recurrent SCNA in human sarcomas that is syntenic to a feline genomic region of probable SCNA in FISS; and (3) significant overlap of the pattern of transcriptional alterations in FISS with the patterns of transcriptional alterations in soft-tissue sarcomas in humans and in dogs. We demonstrated that a protein, BarH-like homeobox 1 (BARX1), has increased expression in FISS cells at the protein level. We identified 11 drugs and four target proteins as potential new therapies for FISS, and validated that one of them (GSK-1059615) inhibits growth of FISS-derived cells in vitro . Conclusions (1) Window-based analysis of mRNA-seq data can uncover SCNAs. (2) The transcriptome of FISS-derived cells is highly consistent with that of FISS tumors. (3) FISS is highly similar to soft-tissue sarcomas in dogs and humans, at the level of gene expression. This work underscores the potential utility of comparative oncology in improving understanding and treatment of FISS. Electronic supplementary material The online version of this article (10.1186/s12885-019-5501-z) contains supplementary material, which is available to authorized users.

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“…Immunotherapy treatments were well-tolerated with only self-limiting local inflammation noted, and 1-year local recurrence rates of 61%, 39%, and 28% were seen in control cats versus those treated with NYVAC human IL-2 or ALVAC feline IL-2, respectively. 49 A later study was performed by Jas et al 50 to further investigate the safety and efficacy of the ALVAC IL-2 immunotherapy. Again, all cats in this study had their tumors excised and were then treated with iridium-based brachytherapy.…”

Section: Treatmentmentioning

confidence: 99%

“…Treatments were well tolerated and no differences in degree of toxicity were noted between low- and high-dose groups. 50 In 2014, the ALVAC feline IL-2 immunotherapy was released in Europe as an adjuvant treatment to surgery to reduce the risk of local tumor recurrence in cats with fibrosarcoma (Merial SAS, Lyon, France). ALVAC feline IL-2 was subsequently conditionally licensed by the United States Department of Agriculture (USDA) in 2015 (Merial Inc., Duluth, GA, USA).…”

Section: Treatmentmentioning

confidence: 99%

Vaccine-associated feline sarcoma: current perspectives

Saba¹

2017

VMRR

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Feline injection site sarcomas (FISS; also known as vaccine-associated sarcomas) have been recognized for >20 years. Although uncommon, these tumors are iatrogenic, and vaccination against rabies and feline leukemia virus is perhaps the most common inciting cause. The exact etiopathogenesis is unknown, but it is widely accepted that inflammation induced by vaccines or other injections likely plays a critical role in tumor development. Injection site sarcomas are extremely locally invasive. Multimodal therapy, incorporating combinations of surgery, radiation therapy, and sometimes chemotherapy or immunotherapy, is recommended. However, tumor recurrences are common even with aggressive treatment, and many cats with FISS ultimately succumb to this devastating disease. While vaccination protocols play an important role in the management and control of infectious disease, veterinarians must be diligent in following established vaccination guidelines to minimize individual patient risk of FISS development. Early tumor detection and client education are also vital in the successful treatment of FISS.

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Adjuvant immunotherapy of feline injection-site sarcomas with the recombinant canarypox virus expressing feline interleukine-2 evaluated in a controlled monocentric clinical trial when used in association with surgery and brachytherapy

Cited by 21 publications

References 28 publications

Role of nuclear factor-kappa B in feline injection site sarcoma

Role of nuclear factor-kappa B in feline injection site sarcoma

Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach

Vaccine-associated feline sarcoma: current perspectives

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