CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA
| Autor: | Paolo Buracco, Soldano Ferrone, Giuseppe La Rosa, Maddalena Arigoni, Federica Cavallo, Federica Riccardo, Alessandra Fiore, Simone Prestigio, Emanuela Maria Morello, Elena Quaglino, Selina Iussich, Stefania Lanzardo, Marina Martano, Raffaella De Maria, Francesca Gattino, Sara Zabarino, Saray Lorda Mayayo, L. Maniscalco, Elena Lardone |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research Electrochemotherapy Melanoma Experimental oral melanoma dog CSPG4 DNA adjuvant electrovaccination Kaplan-Meier Estimate Cancer Vaccines Article Disease-Free Survival DNA vaccination Dogs Antigen Interferon medicine Animals Humans Dog Diseases Melanoma biology business.industry Immunogenicity medicine.disease Oncology Chondroitin Sulfate Proteoglycans CSPG4 Immunology biology.protein Female Mouth Neoplasms Antibody business medicine.drug |
| Zdroj: | Clin Cancer Res |
| Popis: | Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model. Experimental Design: Dogs with stage II–III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated. Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response. Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the “self” antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting. Clin Cancer Res; 20(14); 3753–62. ©2014 AACR. |
| Databáze: | OpenAIRE |
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