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Long-Term Survival of Dogs with Advanced Malignant Melanoma after DNA Vaccination with Xenogeneic Human Tyrosinase
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 st...
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Published in: | Clinical cancer research 2003-04, Vol.9 (4), p.1284 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1078-0432 1557-3265 |