A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy.

Abstract

Simple SummaryDespite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have limited overall survival. Spontaneous canine osteosarcoma shares many molecular similarities with humans, and shows the same aggressive disease course, thereby rendering the dog an effective model for the human disease equivalent. In both species, surgery followed by chemotherapy represents the gold standard treatment. Immunotherapy represents a promising treatment modality. A peptide-based anticancer vaccine was administered to 20 dogs with non-metastatic osteosarcoma as an add-on therapy to standard treatment consisting of limb amputation and adjuvant chemotherapy. Endpoints were to evaluate the efficacy and safety of this combined therapeutic approach. By using a bacterial-based strategy for vaccine development, we report an efficacious induction of an immune response, ultimately translating in improved outcome compared with historical controls receiving standard-of-care treatment. The results of this clinical trial provide promising potential for future management in both humans and dogs with osteosarcoma.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.