Cytokine-Enhanced Vaccine and Suicide Non-Viral Gene Therapy in Advanced Metastatic Melanoma Patients: Two Case Reports

The prognostic for metastatic melanoma is very poor when treated with standard cytotoxic chemotherapies\r\nand it is often refractory to check point inhibitors and/or molecular targets. In this context the development\r\nof new treatments with better efficacy and safety profiles is highly desirable. Based on our successful\r\nexperience applying suicide and immune gene therapy in a veterinary clinical setting, we are proposing its\r\ntranslation to human patients. We are presenting here the first-in-human safety assay of this approach. We\r\nreport two cases of refractory metastatic melanoma. The first-one was a 27-years-old pharyngeal mucosal\r\nmelanoma patient with a primary tumor in his left tonsil. Despite transient slowing down, the disease\r\nsuccessively progressed to radiotherapy, radical surgery, ipilimumab, nivolumab, imatinib and\r\ntemozolomide. The second-one was a 72-years-old malignant melanoma patient with a primary tumor in\r\nhis left hallux. Despite transient slowing down, the disease successively progressed to hallux amputation,\r\ninguinal lymphadenectomy, radiotherapy, interferon-alpha, ipilimumab, pembrolizumab and\r\ntemozolomide. The proposed treatment included local intratumoral suicide gene therapy concomitant with\r\na subcutaneous vaccine composed by allogeneic tumor extracts and liposomes with plasmids bearing IL-2\r\nand GM-CSF genes. The treatment was safe: the only side effects were from mild to moderate and\r\nmanageable: pyrexia, swelling of the injected tumor and partial hair loss (alopecia). Due to disease\r\nprogression both patients were withdrawn from the study before completing the complete series of\r\ninterventions. These preliminary data encourage the completion of further clinical trials to establish the\r\npossible clinical benefit of the proposed approach.