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Updated: Aug 4, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center
P J Bergman1, M A Camps-Palau, J A McKnight
1Donaldson-Atwood Cancer Clinic & Flaherty Comparative Oncology Laboratory, The Animal Medical Center, 510 East 62nd Street, New York, NY 10021, USA. philip.bergman@amcny.org
Introduction:
Canine malignant melanoma (CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. These studies provided the impetus for development of a xenogeneic DNA vaccine program in CMM.
Materials And Methods:
Cohorts of three dogs each received increasing doses of xenogeneic plasmid DNA encoding either human tyrosinase (huTyr; 100/500/1500 mcg), murine GP75 (muGP75; 100/500/1500 mcg), murine tyrosinase (muTyr; 5 dogs each at 100/500 mcg), muTyr+/-HuGM-CSF (9 dogs at 50 mcg muTyr, 3 dogs each at 100/400/800 mcg HuGM-CSF, or 3 dogs each at 50 mcg muTyr with 100/400/800 mcg HuGM-CSF), or 50 mcg MuTyr intramuscularly biweekly for a total of four vaccinations.
Results:
The Kaplan-Meier median survival time (KM MST) for all stage II-IV dogs treated with huTyr, muGP75 and muTyr are 389, 153 and 224 days, respectively. Preliminarily, the KM MST for stage II-IV dogs treated with 50 mcg MuTyr, 100/400/800 mcg HuGM-CSF or combination MuTyr/HuGM-CSF are 242, 148 and >402 (median not reached) days, respectively. Thirty-three stage II-III dogs with loco-regionally controlled CMM across the xenogeneic vaccine studies have a KM MST of 569 days. Minimal to mild pain was noted on vaccination and one dog experienced vitiligo. We have recently investigated antibody responses in dogs vaccinated with HuTyr and found 2- to 5-fold increases in circulating antibodies to human tyrosinase.
Conclusions:
The results of these trials demonstrate that xenogeneic DNA vaccination in CMM: (1) is safe, (2) leads to the development of anti-tyrosinase antibodies, (3) is potentially therapeutic, and (4) is an attractive candidate for further evaluation in an adjuvant, minimal residual disease Phase II setting for CMM.
Insights
Xenogeneic DNA vaccination using tyrosinase family members shows promise for treating canine malignant melanoma (CMM). This approach is safe, elicits anti-tyrosinase antibodies, and offers potential therapeutic benefits for CMM.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Canine Cancer Research
Background:
- Canine malignant melanoma (CMM) is an aggressive cancer with limited treatment options, often becoming metastatic and chemoresistant.
- Previous studies indicate xenogeneic DNA vaccination against tyrosinase family members can induce immune responses and improve survival in CMM.
- This research builds upon prior findings to develop a xenogeneic DNA vaccine program for CMM.
Purpose of the Study:
- To evaluate the safety and efficacy of xenogeneic DNA vaccination in dogs with malignant melanoma.
- To assess immune responses, specifically anti-tyrosinase antibody production, following vaccination.
- To determine the potential therapeutic value of xenogeneic DNA vaccines in prolonging survival for CMM patients.
Main Methods:
- Multiple cohorts of dogs received escalating doses of xenogeneic plasmid DNA encoding human tyrosinase (huTyr), murine GP75 (muGP75), or murine tyrosinase (muTyr).
- Some cohorts received muTyr in combination with granulocyte-macrophage colony-stimulating factor (HuGM-CSF).
- Vaccinations were administered intramuscularly biweekly for a total of four doses.
Main Results:
- Kaplan-Meier median survival times (KM MST) varied by vaccine type, with huTyr, muGP75, and muTyr showing KM MSTs of 389, 153, and 224 days, respectively, for stages II-IV.
- Dogs receiving a combination of muTyr and HuGM-CSF had a KM MST exceeding 402 days (median not reached).
- Dogs with loco-regionally controlled CMM (stages II-III) across studies had a KM MST of 569 days, and anti-tyrosinase antibody levels increased post-vaccination.
Conclusions:
- Xenogeneic DNA vaccination is a safe treatment modality for CMM.
- The vaccination protocol successfully induced anti-tyrosinase antibodies.
- The findings suggest xenogeneic DNA vaccination is a potentially therapeutic approach for CMM and warrants further investigation in Phase II clinical trials for minimal residual disease.
