Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center Journal Article


Authors: Bergman, P. J.; Camps-Palau, M. A.; McKnight, J. A.; Leibman, N. F.; Craft, D. M.; Leung, C.; Liao, J.; Riviere, I.; Sadelain, M.; Hohenhaus, A. E.; Gregor, P.; Houghton, A. N.; Perales, M. A.; Wolchok, J. D.
Article Title: Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center
Abstract: 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. © 2005 Elsevier Ltd. All rights reserved.
Keywords: controlled study; unclassified drug; nonhuman; cancer staging; animals; melanoma; animal experiment; animal model; dog; dog diseases; dogs; dna vaccine; melanoma antigen; monophenol monooxygenase; kaplan meier method; enzyme-linked immunosorbent assay; vaccines, dna; antibody formation; drug delivery system; vitiligo; canine; comparative oncology; xenogeneic; melanoma antigen gp75
Journal Title: Vaccine
Volume: 24
Issue: 21
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2006-05-22
Start Page: 4582
End Page: 4585
Language: English
DOI: 10.1016/j.vaccine.2005.08.027
PUBMED: 16188351
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 68" - "Export Date: 4 June 2012" - "CODEN: VACCD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Polly Gregor
    29 Gregor
  2. Jedd D Wolchok
    665 Wolchok
  3. Miguel-Angel Perales
    378 Perales
  4. Michel W J Sadelain
    456 Sadelain
  5. Isabelle C Riviere
    164 Riviere
  6. Alan N Houghton
    269 Houghton