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- Title
Phase I&Ib Trials of Murine Tyrosinase ± Human GM-CSF DNA Vaccination in Dogs with Advanced Malignant Melanoma.
- Authors
Bergman, P. J.; Camps-Palau, M. A.; McKnight, J. A.; Leibman, N. F.; Novosad, C. A.; Brenn, S.; Ettinger, S. N.; Endicott, M. M.; Finora, K.; Craft, D.; Leung, C.; Liao, J.; Riviere, I.; Hohenhaus, A. E.; Houghton, A.; Perales, M.; Wolchok, J. D.
- Abstract
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. The potency of DNA vaccines can be further enhanced by adding DNA encoding cytokine genes. We have shown in preclinical mouse models that GM-CSF DNA enhances immune responses and tumor protection. These studies provided the impetus for murine tyrosinase(muTyr) ± human GM-CSF(huGM-CSF) DNA vaccination in CMM.Two groups of five dogs each with advanced(WHO stage II-IV) CMM received four biweekly IM injections(100 ug or 500 ug, respectively/vaccination) of plasmid DNA encoding muTyr via the Biojector2000 jet delivery device. Subsequently, three groups of nine dogs each with advanced CMM received four biweekly IM injections of plasmid DNA encoding muTyr(50 ug), huGM-CSF(3 dogs each at 100/400/800 ug) or both.Minimal to mild pain was noted on vaccination and no toxicity or induction of autoimmunity was seen. The KM median survival time was 224 days(100/500 ug muTyr), 278 days(50 ug muTyr), 140 days(huGM-CSF) and>265 days(muTyr&huGM-CSF; 6 dogs still alive).The results of these trials demonstrate that xenogeneic DNA vaccination continues to be a safe and potentially therapeutic modality for CMM. These results also warrant further evaluation of this novel therapeutic in a Phase II setting.
- Subjects
CANCER treatment; MELANOMA; PHENOL oxidase; DNA; CYTOKINES; LABORATORY dogs
- Publication
Veterinary & Comparative Oncology, 2005, Vol 3, Issue 1, p35
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/j.1476-5810.2005.0064g.x