• 1.

    MacEwen EG, Patnaik AK, Harvey HJ, et al. Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest 1986; 4: 397402.

    • Search Google Scholar
    • Export Citation
  • 2.

    Lascelles BDX, Thomson MJ, Dernell WS, et al. Combined dorsolateral and intraoral approach for the resection of tumors of the maxilla in the dog. J Am Anim Hosp Assoc 2003; 39: 294305.

    • Search Google Scholar
    • Export Citation
  • 3.

    Rassnick KM, Ruslander DM, Cotter SM, et al. Use of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989–2000). J Am Vet Med Assoc 2001; 218: 14441448.

    • Search Google Scholar
    • Export Citation
  • 4.

    Boria PA, Murry DJ, Bennett PF, et al. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc 2004; 224: 388394.

    • Search Google Scholar
    • Export Citation
  • 5.

    Proulx DR, Ruslander DM, Dodge RK, et al. A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation. Vet Radiol Ultrasound 2003; 44: 352359.

    • Search Google Scholar
    • Export Citation
  • 6.

    MacEwen EG, Kurzman ID, Vail DM, 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. Clin Cancer Res 1999; 5: 42494258.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bostock DE. Prognosis after surgical excision of canine melanomas. Vet Pathol 1979; 16: 3240.

  • 8.

    Harvey HJ, MacEwen EG, Braun D, et al. Prognostic criteria for dogs with oral melanoma. J Am Vet Med Assoc 1981; 178: 580582.

  • 9.

    Bergman PJ, Wolchok JD. Of mice and men (and dogs): development of a xenogeneic DNA vaccine for canine oral malignant melanoma. Cancer Ther 2008; 6: 817826.

    • Search Google Scholar
    • Export Citation
  • 10.

    Liao JC, Gregor P, Wolchok JD, et al. Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma. Cancer Immun 2006; 6: 817.

    • Search Google Scholar
    • Export Citation
  • 11.

    Bergman PJ, McKnight J, Novosad A, et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res 2003; 9: 12841290.

    • Search Google Scholar
    • Export Citation
  • 12.

    Wang S, Bartido S, Yang G, et al. A role for a melanosome transport signal in accessing the MHC Class II presentation pathway and in eliciting CD4+ T cell responses. J Immunol 1999; 163: 58205826.

    • Search Google Scholar
    • Export Citation
  • 13.

    Goubier A, Fuhrmann L, Forest L, et al. Superiority of needle-free transdermal plasmid delivery for the induction of antigen-specific IFNγ T cell responses in the dog. Vaccine 2008; 26: 21862190.

    • Search Google Scholar
    • Export Citation
  • 14.

    Weber LW, Bowne WB, Wolchok JD, et al. Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest 1998; 102: 12581264.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bowne WB, Srinivasan R, Wolchok JD, et al. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med 1999; 190: 17171722.

  • 16.

    Bergman PJ, Camps-Palau MA, McKnight JA. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006; 24: 45824585.

    • Search Google Scholar
    • Export Citation
  • 17.

    Tang H, Foster NR, Grothey A, et al. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. J Clin Oncol 2010; 28: 19361941.

    • Search Google Scholar
    • Export Citation
  • 18.

    US FDA. Guidance for industry—E10 choice of control group and related issues in clinical trials. May 2001. Available at: www.fda.gov./RegulatoryInformation/Guidances/ucm125802.htm#P590_82931. Accessed Aug 2, 2011.

    • Search Google Scholar
    • Export Citation
  • 19.

    Taylor JMG, Braun TM, Li Z. Comparing an experimental agent to a standard agent: relative merits of a one-arm or randomized two-arm phase II design. Clin Trials 2006; 3: 335348.

    • Search Google Scholar
    • Export Citation
  • 20.

    Wolchok JD, Yuan J, Houghton AN, et al. Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma. Mol Ther 2007; 15: 20442050.

    • Search Google Scholar
    • Export Citation
  • 21.

    Yuan J, Gioffrey YK, Gallardo HF, et al. Safety and immunogenicity of a human and mouse gp 100 DNA vaccine in a phase I trial of patients with melanoma. Cancer Immun 2009; 9: 512.

    • Search Google Scholar
    • Export Citation
  • 22.

    London CA, Malpas PB, Wood-Follis SL, et al. Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009; 15: 38563865.

    • Search Google Scholar
    • Export Citation
  • 23.

    Bergman PJ. Cancer immunotherapy. Top Companion Anim Med 2009; 24: 130136.

Advertisement

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

View More View Less
  • 1 Merial Limited, 1730 Olympic Dr, Athens, GA 30601.
  • | 2 Merial Limited, 1730 Olympic Dr, Athens, GA 30601.
  • | 3 Donaldson-Atwood Cancer Clinic & Flaherty Comparative Oncology Laboratory, The Animal Medical Center, 510 E 62nd St, New York, NY 10021.
  • | 4 Southwest Veterinary Oncology, 141 E Fort Lowell Rd, Tucson, AZ 85705.
  • | 5 Animal Cancer Specialists, 11536 Lake City Way NE, Seattle, WA 98125.
  • | 6 Greater Houston Veterinary Specialists, 1551 Campbell Rd, Houston, TX 77055.
  • | 7 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 8 Southwest Veterinary Oncology, 86 W Juniper Ave, Gilbert, AZ 85233.
  • | 9 Southwest Veterinary Oncology, 86 W Juniper Ave, Gilbert, AZ 85233.
  • | 10 Department of Biostatistics, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912.
  • | 11 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.
  • | 12 Memorial Sloan-Kettering Cancer Center, 1189 1st Ave, New York, NY 10021.

Abstract

Objective—To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs.

Animals—111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved.

Procedures—58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death.

Results—Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because < 50% died of MM before the end of the observation period. No systemic reactions requiring veterinary intervention were associated with vaccination. Local reactions were primarily limited to acute wheal or hematoma formation, mild signs of pain at the injection site, and postvaccination bruising.

Conclusions and Clinical Relevance—Results support the safety and efficacy of the huTyr DNA vaccine in dogs as adjunctive treatment for oral MM.

Impact for Human Medicine—Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

Contributor Notes

Dr. Bergman's present address is BrightHeart Veterinary Centers, 80 Business Park Dr, Ste 110, Armonk, NY 10504. Dr. Jankowski's present address is Southpaws Veterinary Specialist & Emergency Center, 8500 Arlington Blvd, Fairfax, VA 22031. Dr. Jones' present address is Texas Veterinary Oncology, 7958 Shoal Creek Blvd, Austin, TX 78757.

Supported by Merial Limited. Development of the vaccine was supported by NIH P01 CA33049 and Swim Across America.

The authors thank Debra Jarecki, Justin Frost, Stephanie Young-McCannon, Susan Darden, and Dr. Richard Stout for technical assistance.

Address correspondence to Dr. Grosenbaugh (Deborah.Grosenbaugh@merial.com).