Double-blind Placebo-controlled Study With Interleukin-18 and Interleukin-12-encoding Plasmid DNA Shows Antitumor Effect in Metastatic Melanoma in Gray Horses

Müller, Jessika M.V.; Feige, Karsten; Wunderlin, Patrizia; Hödl, Andreas; Meli, Marina L.; Seltenhammer, Monika; Grest, Paula; Nicolson, Lesley; Schelling, C.; Heinzerling, Lucie

doi:10.1097/cji.0b013e3181fe1997

Cited by 44 publications

(46 citation statements)

References 21 publications

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“…CTL generation is favoured in Th1-biased immune responses. A study on plasmid gene therapy coding for equine cytokines IL-12 and -18 induced an in vitro expression of IFNa stimulated by IL-12 (Müller et al 2011). The apparent positive effect of intratumoral Th1 CD4 + T cells (Lowes et al 1997, Wagner et al 1998, Conrad et al 1999) has yet to be proven in EMM.…”

Section: Adaptive Immune Mechanismsmentioning

confidence: 99%

“…The immunogenicity of melanoma antigens has been shown in several species (Speiser et al 2003, Gyorffy et al 2005, Wolchok et al 2007, Yuan et al 2009, Manley et al 2011 and can be presumed for equine melanoma as well due to the antitumoral response seen after immune modifying therapies in EMM-bearing horses (Jeglum 1997, Heinzerling et al 2001, Finocchiaro et al 2009, Müller et al 2011, Phillips and Lembcke 2013. Tumor-associated antibodies (TAA) are a central part in triggering this antitumoral response.…”

Section: Adaptive Immune Mechanismsmentioning

confidence: 99%

“…The therapeutic application of genes coding for human IL-12 or equine IL-12 and -18 in grey horses with EMM resulted in partial tumor regression (Heinzerling et al 2001, Müller et al 2011. In a double-blind placebo-controlled investigation of 26 grey horses bearing melanomas, interleukin-18 encoding plasmid DNA, interleukin-12 encoding plasmid DNA or empty plasmid DNA were injected intratumorally.…”

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

“…Other strategies targeting the inhibition of neoangiogenesis, blockade of oncogene activity or insertion of wild-type tumor suppressor genes (Schmidt-Wolf and SchmidtWolf 1996) have not been reported in EMM treatment. Plasmids coding for antitumoral interleukins (Heinzerling et al 2001, Müller et al 2011 or DNA vectors encoding tumorassociated antigens , Mahlmann et al 2015 have been evaluated for their use in EMM therapy.…”

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

“…One of the advantages of gene therapy is that it may reduce systemic toxicity while improving the specificity of effects (Schmidt-Wolf and SchmidtWolf 1996). Different approaches to cancer gene therapy include inserting suicide genes into the tumor (Finocchiaro et al 2009), enhancing the immunogenicity of the tumor or the antitumoral activity of effector cells (Heinzerling et al 2001, Müller et al 2011, Phillips and Lembkke 2013. Other strategies targeting the inhibition of neoangiogenesis, blockade of oncogene activity or insertion of wild-type tumor suppressor genes (Schmidt-Wolf and SchmidtWolf 1996) have not been reported in EMM treatment.…”

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

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Prospect for immunological therapies of the equine malignant melanoma

Cavalleri¹,

Mählmann²,

Schuberth³

et al. 2015

PHK

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Summary: Although equine melanocytic neoplasms occur frequently, at least in grey horses, their existence is neglected frequently, despite their potentially severe clinical consequences. Immune-based therapies have been investigated in human metastatic melanoma and offer encouraging results. Researchers have recently begun to explore the immunological approach in equine malignant melanoma (EMM) with some success. Therefore, this review aims at giving a short overview of the nature of EMM and providing insight into the immunological basis of melanocytic neoplasms in general. Equine malignant melanoma is a true neoplasm with a genetic basis. Initially they show a slow invasive growth, but they have the potential to metastasize. EMM and human malignant melanomas share various common histopathologic features. For the immune system eradication of the tumor is a challenge. Although solid tumors are often infiltrated with immune cells, they usually do not induce a significant tumor remission. The antitumoral immune response depends on factors of the innate immune system interacting in a coordinated fashion with the adaptive immune system. Antigen-presenting cells, neutrophilic granulocytes, and lymphoid cells may elicit antitumoral effects. This innate response precedes a downstream antigen-specific response. In the tumor microenvironment of solid tumors immune suppressive factors can induce immune escape mechanisms of the tumors. Immunological therapies of EMM include blockage of histamine 2 receptors on melanoma cells and lymphocytes, cancer vaccines and gene therapeutic approaches. This article focuses on the immunological therapeutic approach of EMM and gives an outlook on future implications.

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Section: Adaptive Immune Mechanismsmentioning

confidence: 99%

Section: Adaptive Immune Mechanismsmentioning

confidence: 99%

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

Section: Blockage Of Host Moleculesmentioning

confidence: 99%

See 3 more Smart Citations

Prospect for immunological therapies of the equine malignant melanoma

Cavalleri¹,

Mählmann²,

Schuberth³

et al. 2015

PHK

View full text Add to dashboard Cite

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Administration and detection of gene therapy in horses: A systematic review

Haughan

Ortved

Robinson

2022

Drug Testing and Analysis

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Gene therapy uses genetic modification of cells to produce a therapeutic effect.Defective or missing genes can be repaired or replaced, or gene expression can be modified using a variety of technologies. Repair of defective genes can be achieved using specialized gene editing tools. Gene addition promotes gene expression by introducing synthetic copies of genes of interest (transgenes) into cells where they are transcribed and translated into therapeutic proteins. Protein production can also be modified using therapies that regulate gene expression.Gene therapy is currently prohibited in both human and equine athletes because of the potential to induce production of performance-enhancing proteins in the athlete's body, also referred to as "gene doping." Detection of gene doping is challenging and necessitates development of creative, novel analytical methods for doping control. Methods for detection of gene doping must be specific to and will vary depending on the type of gene therapy. The purpose of this paper is to present the results of a systematic review of gene editing, gene therapy, and detection of gene doping in horses.Based on the published literature, gene therapy has been administered to horses in a large number of experimental studies and a smaller number of clinical cases. Detection of gene therapy is possible using a combination of PCR and sequencing technologies. This summary can provide a basis for discussion of appropriate and inappropriate uses for gene therapy in horses by the veterinary community and guide expansion of methods to detect inappropriate uses by the regulatory community.

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Surgical excision of a malignant metastatic melanoma located in a skeletal muscle of the lateral thorax of a horse

Billi

Karadima

Tyrnenopoulou

et al. 2020

Veterinary Medicine & Sci

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Background A 20‐year‐old grey Warmblood gelding that had history of dermal melanomatosis. Objective To report surgical treatment of a 6‐cm large malignant metastatic melanoma located in the cutaneous trunci muscle of the left lateral thorax of a horse. Methods A 20‐year‐old grey Warmblood gelding was referred for evaluation of a large, rapidly growing, thoracic mass. Clinical examination revealed an ovoid, firm, non‐painful, movable mass, approximately 6 cm in diameter, located in the cutaneous trunci muscle of the left lateral thorax. Multiple melanocytic nodules were also found at the perianal region and ventral tail. Rectal examination, ultrasonography and endoscopy of the respiratory tract revealed no melanomas internally. Haematological and biochemical values were within normal limits. Surgical excision of both the thoracic mass and perianal nodules was the treatment of choice. Histopathology of the distant thoracic mass confirmed the diagnosis of malignant metastatic melanoma secondary to the perineal lesions that were confirmed as dermal melanomatosis. Results The horse recovered uneventfully. Up until 3 years post surgery there was no tumour regrowth at the excision sites. Conclusion Surgical excision of the metastatic melanoma was performed and considered successful, with no gross evidence of tumour reoccurrence. Despite the fact that surgical excision is considered a treatment option regarding equine dermal melanomatosis, there is no previously published study proposing surgical removal of distant malignant metastatic melanocytic masses. This is the first report of a successful surgical excision of a large (6 cm) metastatic melanocytic tumour from the skeletal muscle of the lateral thorax of a horse.

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Double-blind Placebo-controlled Study With Interleukin-18 and Interleukin-12-encoding Plasmid DNA Shows Antitumor Effect in Metastatic Melanoma in Gray Horses

Cited by 44 publications

References 21 publications

Prospect for immunological therapies of the equine malignant melanoma

Prospect for immunological therapies of the equine malignant melanoma

Administration and detection of gene therapy in horses: A systematic review

Surgical excision of a malignant metastatic melanoma located in a skeletal muscle of the lateral thorax of a horse

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