Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK

Verganti, Sara; Berlato, Davide; Blackwood, Laura; Amores-Fuster, I.; Polton, Gerry; Elders, Richard; Doyle, Reina; Taylor, Angela; Murphy, Sue

doi:10.1111/jsap.12613

Cited by 50 publications

(45 citation statements)

References 29 publications

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“…Because of the low statistical power due to small number and group heterogeneity, the authors proposed controlled studies to assess whether the addition of any adjuvant treatment to surgery, including immunogene therapy, is able to significantly prolong survival in cases of canine oral melanomas. A very recent paper[21] analyzing the outcome of 69 canine melanoma patients after human tyrosinase DNA vaccination, reported a median survival time of 455 d, a value that is similar to those published earlier[19,20]. Since the authors observed responses in patients with macroscopic disease, they suggest that the vaccine could be considered as palliative treatment in dogs with remaining tumors or recurrence.…”

Section: Antigen-based Immunogene Therapysupporting

confidence: 68%

Recent clinical trials of cancer immunogene therapy in companion animals

Finocchiaro

Glikin

2017

WJEM

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This mini-review presents the results of veterinary clinical trials on immunogene therapy published from 2014 to 2016. A variety of tumors, among them melanoma (canine and equine), mastocytoma (canine), mammary adenocarcinoma (canine) and fibrosarcoma (feline) were treated by using diverse strategies. Non-viral vectors were usually employed to transfer genes of cytokines, suicide enzymes and/or tumor associated antigens. In general terms, minor or no adverse collateral effects were related to these procedures, and treated patients frequently improved their conditions (better quality of life, delayed or suppressed recurrence or metastatic spread, increased survival). Some of these new methodologies have a promising future if applied as adjuvant treatments of standard approaches. The auspicious results, derived from immunogene therapy studies carried out in companion animals, warrant their imperative usage in veterinary clinical oncology. Besides, they provide a strong preclinical basis (safety assays and proofs of concept) for analogous human clinical trials.

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Section: Antigen-based Immunogene Therapysupporting

confidence: 68%

Recent clinical trials of cancer immunogene therapy in companion animals

Finocchiaro

Glikin

2017

WJEM

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“…Canine melanoma is a chemoresistant tumour and adjuvant chemotherapy using mostly platinum agents failed to show any clinical benefits . In the last decade, the development of a xenogeneic melanoma DNA vaccine has shown some promising results in terms of safety, clinical response and survival, but needs further investigations with randomized controlled trials . Effective systemic therapies, including targeted therapies and immunotherapy are strongly needed to treat this cancer.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Prouteau

Chocteau

Brito

et al. 2019

Vet Comparative Oncology

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Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow-up of 6 months. Epidemiological, clinical and histological data were collected and quantitative-PCR were performed on formalin-fixed paraffin-embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.

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“…The review found that dogs that received the vaccine did not achieve a greater progression-free survival, disease-free interval, or median survival time than dogs that did not receive the vaccine [28]. Similar results were obtained in a study conducted in the UK [29]. The vaccine was shown to induce a B-cell response, which is unlikely to limit melanoma progression.…”

Section: Discussionmentioning

confidence: 60%

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma

Kurupati

Zhou

Xiang

et al. 2018

Cancer Immunol Immunother

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Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8 and CD4 T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8 and CD4 T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.

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Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK

Cited by 50 publications

References 29 publications

Recent clinical trials of cancer immunogene therapy in companion animals

Recent clinical trials of cancer immunogene therapy in companion animals

Prognostic value of somatic focal amplifications on chromosome 30 in canine oral melanoma

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma

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