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

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.

Nanocarriers in Veterinary Medicine: A Challenge for Improving Osteosarcoma Conventional Treatments

“…Two groups of dogs were enrolled in this study: one group received standard treatment, consisting in limb amputation and chemotherapy, and the other group received additional vaccination. The second group demonstrated a significant increase of the period prior to developing metastasis and of survival [79].…”

Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs

“…Multiple bacterial-based anti-cancer therapies have been evaluated in dogs. These include a phase I trial of Salmonella typhimurium in dogs with spontaneous tumors, intra-tumoral injection of Clostridium novyi spores in dogs with spontaneous tumors (largely STSs), and Listeria - and Salmonella -based vaccine strategies in dogs with osteosarcoma ( 278 , 279 , 282 – 284 ). Two vaccine-based treatments for canine OS showed promise (one with immunogenic peptides from Salmonella -infected canine osteosarcoma cells and one with a HER2-targeting Listeria ).…”

“…Two vaccine-based treatments for canine OS showed promise (one with immunogenic peptides from Salmonella-infected canine osteosarcoma cells and one with a HER2-targeting Listeria). Improvements in time to metastasis and survival were seen compared to historical cohorts receiving the standard of care in these preliminary studies (282,284). Bacillus Calmette-Guerin (BCG), a live-attenuated strain of Mycobacterium bovis, is thought to activate macrophages predominantly through TLR-2, although it introduces a massive cytokine response and likely works through other mechanisms as well (285, 286).…”

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

“…These peptides, if used in a vaccine formulation, are capable of eliciting an antitumor response in these model systems [23]. Further, a clinical study by our group documented that a heterologous, anticancer vaccine generated from primary osteosarcoma cells induced a tumor-specific immune response in dogs with appendicular osteosarcoma, significantly prolonging survival compared to dogs receiving the standard of care (SOC) treatment only [24].…”