A chimeric human/dog-DNA vaccine against CSPG4 induces immunity with therapeutic potential in comparative preclinical models of osteosarcoma.

The high mortality rate of osteosarcoma (OSA) patients highlights the requirement of alternative strategies. The young age of patients, as well as the rarity and aggressiveness of the disease, limits opportunities for the robust testing of novel therapies, suggesting the need for valuable preclinical systems. Having previously shown the overexpression of the chondroitin sulfate proteoglycan (CSPG)4 in OSA, herein the functional consequences of its downmodulation in human OSA cells were evaluated in vitro, with a significant impairment of cell proliferation, migration, and osteosphere generation. The potential of a chimeric human/dog (HuDo)-CSPG4 DNA vaccine was explored in translational comparative OSA models, including human xenograft mouse models and canine patients affected by spontaneous OSA. The adoptive transfer of HuDo-CSPG4 vaccine-induced CD8+ T cells and sera in immunodeficient human OSA-bearing mice delayed tumor growth and metastasis development. HuDo-CSPG4 vaccination resulted safe and effective in inducing anti-CSPG4 immunity in OSA-affected dogs, which displayed prolonged survival as compared to controls. Finally, HuDo-CSPG4 was also able to induce a cytotoxic response in a human surrogate setting in vitro. On the basis of these results and the high predictive value of spontaneous OSA in dogs, this study paves the way for a possible translation of this approach to humans.

Palliative repeated electroporations of oral tumours in dogs: A case series.

Electrochemotherapy (ECT) is a highly developed treatment for many solid tumours that provides good local control in 80% of neoplasms in dogs. ECT can be used to treat different types of tumours, particularly as an innovative approach for non-resectable masses. As reported in the literature, electroporation-based treatments are safe, simple, fast and cost-effective treatment alternatives for selected oral and maxillofacial tumours not involving the bone in dogs (e.g., small squamous cell carcinoma or malignant melanoma). In this descriptive retrospective paper, the authors describe the outcome of various types of oral tumours treated with ECT as a palliative first line treatment or as a rescue treatment in dogs with local tumour recurrence. Nineteen dogs were included and treated with at least one session of three electroporations coupled with intravenous administration of bleomycin every 21 days. Tumour size, localization, histotype, stage, recurrence, solid tumour response evaluation criteria (RECIST), local toxicity, progression free survival (PFS) and median survival time (MST) were evaluated. The small population did not allow the analysis of the ECT response by comparing different tumour types; further studies with a larger caseload are needed. However, all dogs, despite the low MST, showed a good local response to treatment with a rapid improvement in quality of life from the first ECT application; no side effects attributable to chemotherapy have been detected and toxicity due to the electroporation was minimal and well tolerated in all dogs.