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A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular
Laura Marconato1, Alessia Melacarne2, Marina Aralla3
1Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, 40064 Bologna, Italy.
Abstract:
Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma.
Insights
A novel peptide-based anticancer vaccine significantly improved survival times for dogs with osteosarcoma. This bacteria-based vaccine, administered alongside standard care, showed no toxicity and induced immune responses, offering a promising new treatment strategy.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Cancer Research
Background:
- Canine osteosarcoma presents a poor prognosis and limited survival rates despite current treatment modalities.
- Novel therapeutic strategies are crucial for improving outcomes in canine osteosarcoma patients.
- Standard of care (SOC) for appendicular osteosarcoma involves limb amputation and adjuvant chemotherapy.
Purpose of the Study:
- To evaluate the antitumor effect and safety of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma.
- To assess the vaccine's impact on time to metastasis (TTM) and tumor-specific survival (TSS) when combined with SOC.
- To investigate vaccine-induced immune responses (T-cell and humoral) and associated toxicity.
Main Methods:
- A clinical trial involving dogs with non-metastatic appendicular osteosarcoma undergoing SOC (amputation and carboplatin chemotherapy).
- Vaccine preparation involved Salmonella-infected canine osteosarcoma cells releasing immunogenic peptides via Cx43 hemichannels.
- Vaccinated dogs received six monthly dermal administrations; a control group received SOC only. TTM and TSS were primary endpoints.
Main Results:
- Vaccine-specific humoral and T-cell responses were observed, correlating with improved tumor-specific survival (TSS).
- No vaccine-associated toxicity was recorded during the study.
- Vaccinated dogs demonstrated significantly longer TTM (308 vs. 240 days) and TSS (621 vs. 278 days) compared to controls.
Conclusions:
- The addition of this bacteria-based vaccination strategy to SOC significantly increased TTM and TSS in dogs with osteosarcoma.
- The peptide-based vaccine is safe and well-tolerated, inducing a long-term tumor-specific immune response.
- This immunotherapy approach holds significant promise for enhancing the management and survival of canine osteosarcoma.
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