Chondroitin sulfate proteoglycan-4: A biomarker and a potential immunotherapeutic target for canine malignant melanoma

Mayayo, Saray Lorda; Prestigio, Simone; Maniscalco, Lorella; Rosa, Giuseppe La; Aricò, Arianna; Maria, Raffaella De; Cavallo, Federica; Ferrone, Soldano; Buracco, Paolo; Iussich, Selina

doi:10.1016/j.tvjl.2011.02.020

Cited by 39 publications

(52 citation statements)

References 34 publications

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“…In particular, human CSPG4 (hCSPG4) displays 82% homology and 88% similarity to its canine counterpart in its amino-acidic sequence. Moreover, the frequency of CSPG4 expression in canine and human melanoma lesions is quite similar, being about 60% (19) and 80% (20), respectively. DNA vaccination has been extensively explored in the field of melanoma immunotherapy, and a number of DNA vaccination clinical trials have been performed in human patients with melanoma; trial results have all been disappointing, probably because of the lack of immunogenicity in DNA vaccines, even when administered with Salmonella typhimurium (21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 85%

“…The present study has evaluated the immunotargeting of CSPG4, a useful diagnostic biomarker of cMM (19) and an attractive oncoantigen (15), in dogs with surgically resected stage II-III CSPG4-positive oral MM. The age and male prevalence of the canine population presented here were in agreement with the literature (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…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). Briefly, a total score ranging from 0 to 8 was assigned to each MM sample by adding the value that represented the proportion of CSPG4 positively stained tumor cells (score from 0 to 5) and the average staining intensity of CSPG4-positive tumor cells (score from 0 to 3).…”

Section: Translational Relevancementioning

confidence: 99%

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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

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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.

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Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Translational Relevancementioning

confidence: 99%

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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

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“…, dysregulation of the Wnt/β-catenin pathway (Han et al, 2013;Larue and Delmas, 2006) and expression of chondroitin sulphate proteoglycan 4 (CSPG4) (Mayayo et al, 2011;Price et al, 2011). Some molecular differences also occur between the species, for example mutation of codon 599 in BRAF, a member of the mitogen-activated protein kinase (MAPK) cascade is a common feature of human cutaneous malignant melanoma and results in elevated kinase activity (Davies et al, 2002), this was not identified in oral CMM samples (Shelly et al, 2005).…”

mentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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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.

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“…Mayayo et al [95] were the first to investigate the expression of chondroitin sulfate proteoglycan (CSPG) 4 in canine MM. It is an early cell-surface progression marker which is highly expressed in about 80 % of human MM where it regulates tumor cell proliferation, migration and invasion [96].…”

Section: Melanomamentioning

confidence: 99%