Long-Term Survival of Dogs with Advanced Malignant Melanoma after DNA Vaccination with Xenogeneic Human Tyrosinase

• Published in: Clinical cancer research 2003-04, Vol.9 (4), p.1284
• Main Authors: Philip J. Bergman, Joanne McKnight, Andrew Novosad, Sarah Charney, John Farrelly, Diane Craft, Michelle Wulderk, Yusuf Jeffers, Michel Sadelain, Ann E. Hohenhaus, Neil Segal, Polly Gregor, Manuel Engelhorn, Isabelle Riviere, Alan N. Houghton, Jedd D. Wolchok
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265

Purpose: Canine malignant melanoma (CMM) is a spontaneous, aggressive, and metastatic neoplasm. Preclinical mouse studies have shown that xenogeneic DNA vaccination with genes encoding tyrosinase family members can induceantibody and cytotoxic T-cell responses, resulting in tumor rejection. These studies provided the rationale for a trial of xenogeneic DNA vaccination in CMM using the human tyrosinase gene. Experimental Design: Three cohorts of three dogs each with advanced (WHO stage II, III, or IV) CMM received four biweekly i.m. injections (dose levels 100, 500, or 1500 μg, respectively/vaccination) of human tyrosinase plasmid DNA i.m. via the Biojector2000 delivery device. Results: Mild local reactions at injection sites were the only toxicities observed, with no signs of autoimmunity. One dog with stage IV disease had a complete clinical response in multiple lung metastases for 329 days. Two dogs with stage IV disease had long-term survivals (421 and 588+ days) in the face of significant bulky metastatic disease, and two other dogs with locally controlled stage II/III disease had long-term survivals (501 and 496 days) with no evidence of melanoma on necropsy. Four other dogs were euthanized because of progression of the primary tumor. The Kaplan-Meier median survival time for all nine dogs was 389 days. Conclusions: The results of this trial demonstrate that xenogeneic DNA vaccination of dogs with advanced malignant melanoma is a safe and potentially therapeutic modality. On the basis of these results, additional evaluation of this novel therapeutic is warranted in locally controlled CMM and advanced human melanoma.