Antitumor effect of electrochemotherapy on osteosarcoma in vitro and in vivo

Osteosarcoma is one of the most common primary bone tumours and there has been no significant progress in long-term tumour control for more than three decades. In recent years, electrochemotherapy has been successfully applied to tumours of different histologies, such as melanomas, basal and squamous cell carcinomas, adenocarcinomas and also bone metastases of various primary cancers. Given the current success rate in different tumour histologies, electrochemotherapy represents a promising approach for the treatment of osteosarcoma. In addition, electrochemotherapy with specific cytotoxic drugs (such as oxaliplatin) induces immunogenic cell death, which has immunomodulatory properties, and thus improves the antitumour response.

In the proposed project, we aim to investigate the effect of electrochemotherapy with bleomycin, cisplatin or oxaliplatin on orthotopic osteosarcoma tumours in mice. The project will evaluate the sensitivity of a mouse osteosarcoma cell line after electroporation with bleomycin, cisplatin or oxaliplatin. Next, we will create 3D models of spheroids, which will also be used to test the sensitivity of these models to electrochemotherapy with bleomycin, cisplatin or oxaliplatin.

We will then establish a method for seeding orthotopic osteosarcoma tumours and determine the pharmacokinetics of bleomycin, cisplatin and oxaliplatin. With the orthotopic osteosarcoma tumour protocol established and the concentration of cytostatics in osteosarcomas determined, we will assess the efficacy of electrochemotherapy in relation to tumour growth delay, which will be monitored by non-invasive bioluminescence imaging.

We expect to successfully establish tumour spheroids that will help to better translate the effects of therapy from in vitro to in vivo levels of research. We hypothesise that ECT will have an anti-tumour effect on orthotopic osteosarcoma tumours and will increase the infiltration of immune cells into primary tumours. Our contribution to science includes the successful establishment of orthotopic tumours in a specific bone microenvironment, which is crucial to understand the changes in the immune cell population of osteosarcoma tumours upon treatment with ECT. This will shed further light on the action of ECT and evaluate it as a potential therapy for the treatment of bone osteosarcomas in the clinic.