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

Deborah A. Grosenbaugh, A. Timothy Leard, Philip J. Bergman, Mary K. Klein, Karri Meleo, Steven Susaneck, Paul R. Hess, Monika K. Jankowski, Pamela D. Jones, Nicole F. Leibman, Maribeth H Johnson, Ilene D. Kurzman, Jedd D. Wolchok

Research output: Contribution to journalArticle

117 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1631-1638
Number of pages8
JournalAmerican Journal of Veterinary Research
Volume72
Issue number12
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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DNA Vaccines
excision
Monophenol Monooxygenase
recombinant vaccines
melanoma
Melanoma
mouth
Dogs
Safety
neoplasms
dogs
Neoplasms
Vaccination
Vaccines
vaccination
vaccines
Injections
Therapeutics
DNA
Kaplan-Meier Estimate

ASJC Scopus subject areas

  • veterinary(all)

Cite this

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. / Grosenbaugh, Deborah A.; Leard, A. Timothy; Bergman, Philip J.; Klein, Mary K.; Meleo, Karri; Susaneck, Steven; Hess, Paul R.; Jankowski, Monika K.; Jones, Pamela D.; Leibman, Nicole F.; Johnson, Maribeth H; Kurzman, Ilene D.; Wolchok, Jedd D.

In: American Journal of Veterinary Research, Vol. 72, No. 12, 01.01.2011, p. 1631-1638.

Research output: Contribution to journalArticle

Grosenbaugh, DA, Leard, AT, Bergman, PJ, Klein, MK, Meleo, K, Susaneck, S, Hess, PR, Jankowski, MK, Jones, PD, Leibman, NF, Johnson, MH, Kurzman, ID & Wolchok, JD 2011, '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', American Journal of Veterinary Research, vol. 72, no. 12, pp. 1631-1638. https://doi.org/10.2460/ajvr.72.12.1631
Grosenbaugh, Deborah A. ; Leard, A. Timothy ; Bergman, Philip J. ; Klein, Mary K. ; Meleo, Karri ; Susaneck, Steven ; Hess, Paul R. ; Jankowski, Monika K. ; Jones, Pamela D. ; Leibman, Nicole F. ; Johnson, Maribeth H ; Kurzman, Ilene D. ; Wolchok, Jedd D. / 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. In: American Journal of Veterinary Research. 2011 ; Vol. 72, No. 12. pp. 1631-1638.
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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.",
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AU - Leard, A. Timothy

AU - Bergman, Philip J.

AU - Klein, Mary K.

AU - Meleo, Karri

AU - Susaneck, Steven

AU - Hess, Paul R.

AU - Jankowski, Monika K.

AU - Jones, Pamela D.

AU - Leibman, Nicole F.

AU - Johnson, Maribeth H

AU - Kurzman, Ilene D.

AU - Wolchok, Jedd D.

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N2 - 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.

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