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

Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78-1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75-1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non-vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.

[1]  S. Withrow,et al.  Withrow & Macewen's Small Animal Clinical Oncology , 2019 .

[2]  M. Martano,et al.  PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis , 2017, Veterinary and comparative oncology.

[3]  L. Marconato,et al.  Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma. , 2016, Veterinary and comparative oncology.

[4]  S. North,et al.  A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma , 2016, The Journal of veterinary medical science.

[5]  H. Sakai,et al.  Outcomes of dogs undergoing radiotherapy for treatment of oral malignant melanoma: 111 cases (2006-2012). , 2015, Journal of the American Veterinary Medical Association.

[6]  P. Buracco,et al.  Perspectives on the design of clinical trials for targeted therapies and immunotherapy in veterinary oncology. , 2015, Veterinary journal.

[7]  M. Kiupel,et al.  Defining the Pharmacodynamic Profile and Therapeutic Index of NHS-IL12 Immunocytokine in Dogs with Malignant Melanoma , 2015, PloS one.

[8]  R. Lobetti,et al.  Use of the melanoma vaccine in 38 dogs: The South African experience , 2015, Journal of the South African Veterinary Association.

[9]  L. Finocchiaro,et al.  Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma. , 2015, Human gene therapy.

[10]  G. Ciliberto,et al.  Electro-gene-transfer as a new tool for cancer immunotherapy in animals. , 2014, Veterinary and comparative oncology.

[11]  D. Worley,et al.  Outcome following curative-intent surgery for oral melanoma in dogs: 70 cases (1998-2011). , 2014, Journal of the American Veterinary Medical Association.

[12]  L. Finocchiaro,et al.  Clinical Trials of Immunogene Therapy for Spontaneous Tumors in Companion Animals , 2014, TheScientificWorldJournal.

[13]  Y. Okamoto,et al.  Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells , 2014, SpringerPlus.

[14]  R. Mancini,et al.  Xenogene vaccination in the therapy of cancer , 2014, Expert opinion on biological therapy.

[15]  P. Buracco,et al.  Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012). , 2014, Journal of the American Veterinary Medical Association.

[16]  M. Bear,et al.  Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines , 2014, BMC Veterinary Research.

[17]  R. Rebhun,et al.  Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines. , 2014, Research in veterinary science.

[18]  S. Ferrone,et al.  CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA , 2014, Clinical Cancer Research.

[19]  T. Osaki,et al.  Non-surgical treatment of canine oral malignant melanoma: A case study of the application of complementary alternative medicine , 2014, Oncology letters.

[20]  B. Kitchell,et al.  Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision. , 2014, Veterinary and comparative oncology.

[21]  M. Pennell,et al.  Preclinical Evaluation of the Novel, Orally Bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Spontaneous Canine Cancer: Results of a Phase I Study , 2014, PloS one.

[22]  J. Hauptman,et al.  A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma. , 2013, Veterinary and comparative oncology.

[23]  P. Mayhew,et al.  Results of surgical excision and evaluation of factors associated with survival time in dogs with lingual neoplasia: 97 cases (1995-2008). , 2013, Journal of the American Veterinary Medical Association.

[24]  B. Kaser-Hotz,et al.  [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study]. , 2013, Schweizer Archiv fur Tierheilkunde.

[25]  A. Herzog,et al.  Kombinierte Anwendung von Strahlentherapie und DNS Tumor Vakzine zur Behandlung des oralen malignen Melanoms beim Hund: Eine Pilotstudie , 2013 .

[26]  M. Cooper,et al.  Malignant melanoma in 63 dogs (2001–2011): the effect of carboplatin chemotherapy on survival , 2013, New Zealand veterinary journal.

[27]  Gui-yuan Li,et al.  CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma , 2011, Pigment cell & melanoma research.

[28]  J. Wolchok,et al.  Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. , 2011, American journal of veterinary research.

[29]  S. Ferrone,et al.  Chondroitin sulfate proteoglycan-4: a biomarker and a potential immunotherapeutic target for canine malignant melanoma. , 2011, Veterinary journal.

[30]  N. Sardesai,et al.  Electroporation delivery of DNA vaccines: prospects for success. , 2011, Current opinion in immunology.

[31]  M. Miller,et al.  Immunohistochemical Identification of Canine Melanocytic Neoplasms With Antibodies to Melanocytic Antigen PNL2 and Tyrosinase , 2011, Veterinary pathology.

[32]  M. Kiupel,et al.  Prognostic Evaluation of Ki67 Threshold Value in Canine Oral Melanoma , 2011, Veterinary pathology.

[33]  M. Kiupel,et al.  Immunohistochemical Diagnosis of Canine Oral Amelanotic Melanocytic Neoplasms , 2011, Veterinary pathology.

[34]  M. Kiupel,et al.  Prognostic Markers for Canine Melanocytic Neoplasms , 2011, Veterinary pathology.

[35]  Richard Heller,et al.  Electroporation gene therapy preclinical and clinical trials for melanoma. , 2010, Current gene therapy.

[36]  V. Grieco,et al.  Immunohistochemical Investigation of PNL2 Reactivity of Canine Melanocytic Neoplasms and Comparison with Melan A , 2010, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[37]  Martin A. Cheever,et al.  The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research , 2009, Clinical Cancer Research.

[38]  D. Worley,et al.  A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology. , 2009, Veterinary and comparative oncology.

[39]  Richard Heller,et al.  Electroporation for the delivery of DNA-based vaccines and immunotherapeutics: current clinical developments. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[40]  D. G. Esplin Survival of Dogs Following Surgical Excision of Histologically Well-differentiated Melanocytic Neoplasms of the Mucous Membranes of the Lips and Oral Cavity , 2008, Veterinary pathology.

[41]  G. Maglennon,et al.  Oral malignant melanoma - the effect of coarse fractionation radiotherapy alone or with adjuvant carboplatin therapy. , 2005, Veterinary and comparative oncology.

[42]  S. Ferrone,et al.  Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms , 2004, The Journal of cell biology.

[43]  P. Snyder,et al.  Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. , 2004, Journal of the American Veterinary Medical Association.

[44]  R. Dodge,et al.  A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation. , 2003, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[45]  R. Packer,et al.  Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001). , 2003, Journal of the American Veterinary Medical Association.

[46]  J. Wolchok,et al.  Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[47]  J. Robertson,et al.  Lymph Node Staging of Oral and Maxillofacial Neoplasms in 31 Dogs and Cats , 2002, Journal of veterinary dentistry.

[48]  R. M. Gamblin,et al.  Use of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989-2000). , 2001, Journal of the American Veterinary Medical Association.

[49]  M. Miller,et al.  Retrospective Study of 338 Canine Oral Melanomas with Clinical, Histologic, and Immunohistochemical Review of 129 Cases , 2000, Veterinary pathology.

[50]  R. Dubielzig,et al.  Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[51]  R. Dubielzig,et al.  Development of human granulocyte-macrophage colony-stimulating factor-transfected tumor cell vaccines for the treatment of spontaneous canine cancer. , 1998, Human gene therapy.

[52]  T. Potter,et al.  In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma. , 1998, The Journal of clinical investigation.

[53]  B. Madewell,et al.  Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation. , 1997, Journal of the American Veterinary Medical Association.

[54]  P. Kourilsky,et al.  Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2. , 1996, Gene therapy.

[55]  L. Blackwood,et al.  Radiotherapy of oral malignant melanomas in dogs. , 1996, Journal of the American Veterinary Medical Association.

[56]  P. Catton,et al.  0-7-21 radiation therapy for the treatment of canine oral melanoma. , 1994, Journal of veterinary internal medicine.

[57]  D. M. Brown,et al.  Intralesional implant for treatment of primary oral malignant melanoma in dogs. , 1994, Journal of the American Veterinary Medical Association.

[58]  D. Matthiesen,et al.  Hemimaxillectomy for the treatment of oral tumors in 69 dogs. , 1992, Veterinary surgery : VS.

[59]  D. Matthiesen,et al.  Results of partial mandibulectomy for the treatment of oral tumors in 142 dogs. , 1991, Veterinary surgery : VS.

[60]  M. Dewhirst,et al.  Local control and distant metastases in primary canine malignant melanomas treated with hyperthermia and/or radiotherapy. , 1985, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[61]  S. Withrow,et al.  Prognostic criteria for dogs with oral melanoma. , 1981, Journal of the American Veterinary Medical Association.

[62]  T. Osaki,et al.  Clinical systemic lupeol administration for canine oral malignant melanoma. , 2015, Molecular and clinical oncology.

[63]  K. Hahn,et al.  Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997). , 2003, Journal of veterinary internal medicine.

[64]  B. Madewell,et al.  Preclinical study of sequential tumor necrosis factor and interleukin 2 in the treatment of spontaneous canine neoplasms. , 1991, Cancer research.

[65]  R. Matus,et al.  Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. , 1986, Cancer investigation.

[66]  C. G. Darlington Oral tumors. , 1953, New York state journal of medicine.