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A Phase 2, Single-Arm, Open-Label Clinical Trial on Adjuvant Peptide-Based Vaccination in Dogs with Aggressive Hemangiosarcoma Undergoing Surgery and Chemotherapy

SIMPLE SUMMARY: Canine hemangiosarcoma shares many clinical, histologic and molecular features with human angiosarcoma. Thus, the dog represents a powerful and alternative model of spontaneously occurring hemangiosarcoma for comparative studies and developmental therapeutic investigation. In both sp...

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Detalles Bibliográficos
Autores principales: Marconato, Laura, Tiraboschi, Luca, Aralla, Marina, Sabattini, Silvia, Melacarne, Alessia, Agnoli, Chiara, Balboni, Andrea, Salvi, Marta, Foglia, Armando, Punzi, Sofia, Romagnoli, Noemi, Rescigno, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486958/
https://www.ncbi.nlm.nih.gov/pubmed/37686485
http://dx.doi.org/10.3390/cancers15174209
Descripción
Sumario:SIMPLE SUMMARY: Canine hemangiosarcoma shares many clinical, histologic and molecular features with human angiosarcoma. Thus, the dog represents a powerful and alternative model of spontaneously occurring hemangiosarcoma for comparative studies and developmental therapeutic investigation. In both species, surgery and adjuvant dose-intense chemotherapy represent the gold standard treatment. Several attempts have been made to improve patient outcomes. Novel clinical protocols have been designed, and different pharmacological and surgical approaches have been tested. However, hemangiosarcoma treatment remains an unmet medical need. Immunotherapy has emerged as a promising strategy. An anticancer vaccine was administered to 28 dogs with biologically aggressive hemangiosarcoma in combination with the standard treatment. The endpoints of the study were efficacy and safety. In addition to the tolerability of the vaccine, the induction of immune responses was reported, ultimately leading to improved outcomes compared with historical controls receiving the standard of care treatment only. The current findings provide promising potential for future management in both species. ABSTRACT: To test the antitumor effect and safety of peptide-based anticancer vaccination in dogs with hemangiosarcoma undergoing the standard of care (SOC; surgery and doxorubicin), canine hemangiosarcoma cells were infected with Salmonella typhi Ty21a to release immunogenic endoplasmic reticulum stress-related peptides into the extracellular milieu via CX43 hemichannels opening. The infected tumor cell secretome constituted the vaccine. Following the SOC, dogs with biologically aggressive hemangiosarcoma were vaccinated a total of five times, once every 3 weeks, and were followed up with serial imaging. A retrospective population of dogs undergoing the SOC alone served as controls. The primary endpoints were the time to progression (TTP) and overall survival (OS), and the secondary endpoints were toxicity and immune responses. A total of 28 dogs were vaccinated along with the SOC, and 32 received only the SOC. A tumor-specific humoral response along with a vaccine-specific T-cell response was observed. Toxicity did not occur. The TTP and OS were significantly longer in vaccinated versus unvaccinated dogs (TTP: 195 vs. 160 days, respectively; p = 0.001; OS: 276 vs. 175 days, respectively; p = 0.002). One-year survival rates were 35.7% and 6.3% for vaccinated and unvaccinated dogs, respectively. In dogs with hemangiosarcoma undergoing the SOC, the addition of a peptide-based vaccine increased the TTP and OS, while maintaining a safe profile. Moreover, vaccinated dogs developed a tumor-specific response, supporting the feasibility of future phase three studies.