Prolongation of survival of dogs with oral malignant melanoma treated by<i>en bloc</i>surgical resection and adjuvant<scp>CSPG4</scp>‐antigen electrovaccination

Piras, Lisa Adele; Riccardo, Federica; Iussich, Selina; Maniscalco, Lorella; Gattino, Francesca; Martano, Marina; Morello, Emanuela; Mayayo, Saray Lorda; Rolih, Valeria; Garavaglia, F.; Maria, Raffaella De; Lardone, Elena; Collivignarelli, Francesco; Mignacca, D.; Giacobino, Davide; Ferrone, Soldano; Cavallo, Federica; Buracco, Paolo

doi:10.1111/vco.12239

Cited by 44 publications

(68 citation statements)

References 61 publications

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“…interleukin-2 (IL-2), Corynebacterium parvum, granulocyte-macrophage colony-stimulating factor (GM-CSF), chondroitin sulfate proteoglycan-4 (Bianco et al, 2003;Dow et al, 1998;Macewen et al, 1999;MacEwen et al, 1986;Piras et al, 2017;Thamm et al, 2010), and not reached in one study (Finocchiaro and Glikin, 2012). A xenogenic human DNAencoding tyrosinase protein vaccine (Oncept™, Merial®, Duluth, GA, U.S.A.) was developed for the adjuvant treatment of stage II to IV OMMs (Grosenbaugh et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

A combination of electrochemotherapy, gene electrotransfer of plasmid encoding canine IL-12 and cytoreductive surgery in the treatment of canine oral malignant melanoma

Milevoj

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Nemec

et al. 2019

Research in Veterinary Science

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The aim of this study was to evaluate the safety and efficacy of the combination of electrochemotherapy (ECT) with bleomycin and gene electrotransfer (GET) of plasmid encoding canine interleukin 12 (IL-12) for the treatment of canine oral malignant melanoma (OMM). Our focus was to determine the effect of the treatment on achieving local tumor control and stimulation of an antitumor immune response. Nine dogs with histologically confirmed OMM stage I to III were included in a prospective, nonrandomized study. The dogs were treated with a combination of cytoreductive surgery, ECT and IL-12 GET, which was repeated up to five times, depending on the clinical response to the treatment, evaluated according to the followup protocol (7, 14 and 28 days after, the last treatment). One month after treatment, the objective response (OR) rate was 67% (6/9). Median survival time (MST) was 6 months and, even though the disease progressed in 8/9 patients at the end of the observation period (2 to 22 months), four animals were euthanized due to tumor-unrelated reasons. In addition, we observed a decline in the percentage of regulatory T cells (Treg) in the peripheral blood in the course of the treatment, which could be attributed to a systemic antitumor response to IL-12 GET. The results of this study suggest that a combination of ECT and IL-12 GET may be beneficial for dogs with OMM, especially when other treatment approaches are not acceptable due to their invasiveness or cost.

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Section: Discussionmentioning

confidence: 99%

A combination of electrochemotherapy, gene electrotransfer of plasmid encoding canine IL-12 and cytoreductive surgery in the treatment of canine oral malignant melanoma

Milevoj

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Nemec

et al. 2019

Research in Veterinary Science

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“…In the majority of studies published on head and neck cancers in dogs, the completeness of histologic excision is not reported, included as descriptive statistics only and not analysed, or analysed for survival outcomes but not local tumour control …”

Section: Clinical Relevance Of Histologic Margins: Assessing the Riskmentioning

confidence: 99%

“…In the majority of studies published on head and neck cancers in dogs, the completeness of histologic excision is not reported, 108 included as descriptive statistics only and not analysed, 109,110 or analysed for survival outcomes but not local tumour control. 20,22,34,[111][112][113] In a study of 21 dogs with surgically treated oral squamous cell carcinoma, 28 histologic margins were defined as incomplete, close (HTFMs ≤2 mm), and complete (HTFMs >2 mm). Histologic margins were incomplete in two dogs, narrow in four dogs and complete in 15 dogs; local recurrence was reported in one dog with incomplete histologic excision and no dogs with either narrow or complete histologic excisions.…”

Section: Head and Neck Cancersmentioning

confidence: 99%

Histologic margins and the residual tumour classification scheme: Is it time to use a validated scheme in human oncology to standardise margin assessment in veterinary oncology?

Liptak¹

2019

Vet Comparative Oncology

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There is no consensus on the definition of a complete histologic excision in veterinary oncology; many definitions have been used in various studies, but these have been arbitrarily selected with no apparent justification. The residual tumour classification scheme, where a complete histologic excision is defined as a histologic tumour‐free margin >0 mm, has been used for >40 years in human oncology by all of the major clinical staging organizations and is considered highly prognostic for the vast majority of malignant tumours in people. Because of the widespread use of the residual tumour classification scheme both clinically and in research studies, this standardized approach permits better communication between clinicians, an evidence‐based decision‐making process for adjuvant treatment options following surgical resection, minimizes exposing patients to unnecessary adjuvant treatments and a better ability to compare local tumour control for specific tumours between different studies. The adoption of the residual tumour classification scheme in veterinary oncology would likely achieve similar outcomes and minimize the prevalent confusion within the veterinary community, amongst both general practitioners and specialists, regarding the definition of what constitutes a complete histologic excision.

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“…; Piras et al . ) and formulations (Kutzler et al . ) and the need for a vaccine to mediate a rapid immune response to a recent global health concern (Larocca et al .…”

Section: Discussionmentioning

confidence: 99%

“…A larger study could then compare anti-melanoma activity of the huTYR vaccine delivered either by microseeding or by the current Oncept â delivery method of intramuscular injection. The number of ongoing DNA vaccine clinical trials (ClinicalTrials.gov 2016), the need for development of novel DNA vaccine delivery platforms (DeMuth et al 2013;Piras et al 2016) and formulations (Kutzler et al 2016) and the need for a vaccine to mediate a rapid immune response to a recent global health concern (Larocca et al 2016; Morrison 2016), suggest that improvements in DNA vaccine delivery strategies are relevant for today's healthcare. The advent of additional canine-specific reagents for testing in dogs, including anti-PD1 antibody, will allow for study of combination therapies with DNA microseeding.…”

Section: Discussionmentioning

confidence: 99%

Pilot study of safety and feasibility of DNA microseeding for treatment of spontaneous canine melanoma

Zuleger

Kang

Ranheim

et al. 2017

Veterinary Medicine & Sci

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Spontaneous canine malignant melanoma provides an excellent pre‐clinical model to study DNA vaccines for melanoma immunotherapy. A USDA‐approved xenogeneic human tyrosinase (huTYR) plasmid DNA vaccine delivered intramuscularly induces detectable immune responses and has clinical activity in some dogs with melanoma. The objective of this pilot study was to evaluate the feasibility, safety and immunogenicity of huTYR plasmid DNA administered to the skin via microseeding in dogs with spontaneous melanoma. DNA microseeding utilizes a modified tattooing device as an alternate and potentially more potent delivery method for DNA immunization. DNA was delivered to shaved inner thigh skin of six companion dogs with melanoma approximately every 14 days for a planned total of four vaccination time points. An anti‐huTYR ELISA was used to test pre‐ and post‐treatment sera. Biopsies of treated skin were obtained for detection of huTYR transgene expression. DNA microseeding was well tolerated with no significant toxicity detected beyond local site irritation, and there were no signs of autoimmunity. huTYR‐expressing cells were observed in biopsies of huTYR DNA microseeding sites. Increased humoral anti‐huTYR antibodies were seen in two of five evaluable dogs following microseeding compared to baseline. DNA microseeding is well tolerated in companion dogs with melanoma. Further investigation is needed to determine if combining DNA microseeding with other immunotherapy regimens potentiates this delivery platform for cancer immunotherapy.

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Prolongation of survival of dogs with oral malignant melanoma treated byen blocsurgical resection and adjuvantCSPG4‐antigen electrovaccination

Cited by 44 publications

References 61 publications

A combination of electrochemotherapy, gene electrotransfer of plasmid encoding canine IL-12 and cytoreductive surgery in the treatment of canine oral malignant melanoma

A combination of electrochemotherapy, gene electrotransfer of plasmid encoding canine IL-12 and cytoreductive surgery in the treatment of canine oral malignant melanoma

Histologic margins and the residual tumour classification scheme: Is it time to use a validated scheme in human oncology to standardise margin assessment in veterinary oncology?

Pilot study of safety and feasibility of DNA microseeding for treatment of spontaneous canine melanoma

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