A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma

Ottnod, J. M.; Smedley, Rebecca C.; Walshaw, Richard; Hauptman, J. G.; Kiupel, Matti; Obradovich, Joyce E.

doi:10.1111/vco.12057

Cited by 108 publications

(117 citation statements)

References 10 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…The melanoma specific median survival time was not reached (Grosenbaugh et al, 2011). In contrast to these findings, Ottnod and co-workers retrospectively analysed 22 vaccinees and compared these to 23 non-vaccinees with oral CMM (Ottnod et al, 2013). When comparing dogs with stage II and III disease, neither progression free survival (PFS) nor overall survival was significantly different for vaccinees compared to nonvaccinees.…”

Section: Early Evidence Supporting Oncept™mentioning

confidence: 86%

“…Prospective randomised clinical trials are considered "gold standard" for assessing the efficacy of a new pharmaceutical agent, partly as they avoid temporal bias between groups such as changes to primary tumour management, stage migration and grade inflation (Sahora and Khanna, 2010;Vail, 2007). The author of the editorial correctly raised concerns regarding study size for the Ottnod paper (Ottnod et al, 2013) and the level of censoring in the Grosenbaugh study (Grosenbaugh et al, 2011) (it was impossible to derive a melanoma specific median survival time for vaccinees as more than half of these dogs were censored from this analysis) (Vail, 2013). A subsequently published case series of dogs with oral CMM treated with surgery found no survival benefit in a group that received adjuvant vaccination compared to surgery alone (Boston et al, 2014).…”

Section: Early Evidence Supporting Oncept™mentioning

confidence: 99%

See 1 more Smart Citation

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

View full text Add to dashboard Cite

Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

show abstract

Section: Early Evidence Supporting Oncept™mentioning

confidence: 86%

Section: Early Evidence Supporting Oncept™mentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

View full text Add to dashboard Cite

show abstract

“…Those margins with tumor cells reaching the dye were considered as incomplete, whereas those with no evidence of tumor cells within at least 1 mm from the cut surface were considered as "clean" margins. Samples were also immunohistochemically tested for Ki67 expression (polyclonal Ki67 antibody-A-047; DAKO), mitotic index, and nuclear atypia (25,32,33). Immunohistochemical analyses of CSPG4 expression on MM samples were performed as previously described (19).…”

Section: Translational Relevancementioning

confidence: 99%

“…This represents the first approved anticancer vaccine and is meant for the treatment of cMM. However, its therapeutic efficacy has been recently questioned (25).…”

Section: Introductionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

show abstract

“…Treatment of oral melanomas utilizes the surgical excision-resection (Bradley et al, 1984;Culp et al, 2013;Felizzola et al, 2002;Kosovsky et al, 1991;Wallace et al, 1992) and/or radiation therapy ( Proulx et al, 2003;Freeman et al, 2003), chemotherapy with carboplatin (Brockley et al, 2013;Freeman et al, 2003), immunotherapyvaccines with dendritic cells (Grosenbaugh et al, 2011;Ottnod et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Dogs With Oral Melanoma Recurrence by Diode Laser Excision

Igna¹,

Bumb²,

Sicoe³

et al. 2016

BUASVMCN-VM

View full text Add to dashboard Cite

Introduction: Treatment of oral melanomas utilizes the surgical excision-resection (Culp et al., 2013) and/or radiation therapy (Proulx et al., 2003), chemotherapy with carboplatin (Brockley et al., 2013), immunotherapy (Ottnod et al., 2013). Treatment based on surgical excision is usually palliative (Freeman et al., 2003). Aims: In the literature even though there are data concerning the prognosis of oral melanomas in dogs after surgery, are missing data after laser excision. Taking into account these findings we wished to present our experience regarding three cases of oral melanoma recurrence and immediate and long term laser surgery results. Materials and Methods: The casuistry consisted of three dogs with recurrent oral malignant melanomas, subjected to surgical reintervention. The initial diagnosis was melanotic melanoma in stage I or II. The animals were brought back at different time intervals from originally excision with electric scalpel. Before reintervention, dogs were subjected to clinical, paraclinical exam and biopsy. Excision of the tumor mass was made with an optical fiber hawing a diameter of 400µm, at a power of 10W and a wavelength of 940 nm with a diode laser. At 1, 2, 3, 6 and 12 months after laser reintervention the dogs were reexamined. Results: Average time in which appeared canine oral melanoma relapse was 58.6 days. After reexamination all cases where reinstatement in stage I. Operators times were held in conditions of comfort with wide access, minimum bleeding, effective hemostasis. After surgery at 24 hours on the intervention place a slight local redness, without swelling and bleeding was observed. Palpation revealed initially also a slight local sensitivity which completely disappeared in 48 hours. There were no grasping and chewing disturbances. Macroscopic healing occurred in 7-9 days. At last recheck performed at 12 months there were no evidences of tumour recurrence or metastasis. Conclusion: Diode laser excision of oral malignant melanoma in dogs can be an alternative palliative procedure to invasive surgical resection procedures. The average of free recurrence and metastasis time after laser surgery has exceeded 360 days in these three cases.

show abstract

A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma

Cited by 108 publications

References 10 publications

Cancer immunology and canine malignant melanoma: A comparative review

Cancer immunology and canine malignant melanoma: A comparative review

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Treatment of Dogs With Oral Melanoma Recurrence by Diode Laser Excision

Contact Info

Product

Resources

About