Xenogeneic Murine Tyrosinase DNA Vaccine for Malignant Melanoma of the Digit of Dogs

Abstract

Background: Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma.Objectives/Hypothesis: Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma.Animals: Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Methods: Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Results: Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P o .0001). Forty-eight percent of the dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving 4952, 41,093, 321, and 76 days, respectively.Conclusions and Clinical Importance: The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system.

Comparative oncology: what dogs and other species can teach us about humans with cancer

“…Dogs also develop melanoma, and similarly to all the other cancers discussed in this review, these melanocytic canine tumours will very closely resemble human melanoma, emphasizing the beneficial role of the canine preclinical model in studying both UV and non-UV pathways in melanoma [20,146]. Furthermore, the dog has been extremely useful for clinical trials and has contributed to a phase I study for DNA vaccination with xenogeneic human tyrosinase for advanced malignant melanoma [147][148][149][150][151]. Poorman et al [152] used aCGH profiling to compare cutaneous melanomas (often benign) with the more aggressive oral mucosal form.…”

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up

“…[1][2][3] We have widely discussed the potential of comparative cancer gene therapy as a preclinical phase for human clinical trials. 5 Different gene therapy approaches have been reported for canine spontaneous melanoma such as: (i) ex vivo human interleukin-2 (hIL-2) producing xenogeneic cells, 6 human granulocytemacrophage colony-stimulating factor (hGM-CSF) producing autologous tumor cells, 7 human gp100 producing allogeneic tumor cells; 8 and (ii) in vivo gene transfer of enterotoxin-B plus GM-CSF, 9 xenogeneic human 10 or murine 11 tyrosinase, human FasL, 12 IL-12 (ref. 13) and CD40 ligand.…”

Immunotherapy in Veterinary Oncology

“…[106][107][108] To further highlight xenogeneic DNA vaccination as a platform to target other possible antigens for other histologies, the authors and colleagues have completed a phase I trial of murine CD20 for dogs with B-cell lymphoma; will be initiating additional trials, such as a phase I trial of rat HER2 and a phase II trial of murine CD20; and have also investigated the efficacy of local tumor control and use of xenogeneic DNA vaccination in dogs with digit malignant melanoma. 109 These investigations led to the development of a canine digit melanoma staging scheme and found an improvement in survival compared with historical outcomes with digit amputation only. The authors and colleagues also documented a decreased prognosis for dogs with advanced stage disease and/or increased time from digit amputation to the start of vaccination.…”