article = {COR-2020-5-102}
title = {Cytokine-Enhanced Vaccine and Suicide Non-Viral Gene Therapy in Advanced Metastatic Melanoma Patients: Two Case Reports}
journal = {Clinical Oncology and Research}
year = {2020}
issn = {2613-4942}
doi = {http://dx.doi.org/10.31487/j.COR.2020.05.02}
url = {https://www.sciencerepository.org/cytokine-enhanced-vaccine-and-suicide-non-viral-gene-therapy-in_COR-2020-5-102 
author = {Gerardo C.  Glikin,Heliana L.  Hernández-Herrera,Liliana M. E. Finocchiaro,Ventura A.  Simonovich,}
keywords = {Metastatic melanoma, gene therapy, suicide gene, cytokine, immunotherapy, case report}
abstract ={The prognostic for metastatic melanoma is very poor when treated with standard cytotoxic chemotherapies
and it is often refractory to check point inhibitors and/or molecular targets. In this context the development
of new treatments with better efficacy and safety profiles is highly desirable. Based on our successful
experience applying suicide and immune gene therapy in a veterinary clinical setting, we are proposing its
translation to human patients. We are presenting here the first-in-human safety assay of this approach. We
report two cases of refractory metastatic melanoma. The first-one was a 27-years-old pharyngeal mucosal
melanoma patient with a primary tumor in his left tonsil. Despite transient slowing down, the disease
successively progressed to radiotherapy, radical surgery, ipilimumab, nivolumab, imatinib and
temozolomide. The second-one was a 72-years-old malignant melanoma patient with a primary tumor in
his left hallux. Despite transient slowing down, the disease successively progressed to hallux amputation,
inguinal lymphadenectomy, radiotherapy, interferon-alpha, ipilimumab, pembrolizumab and
temozolomide. The proposed treatment included local intratumoral suicide gene therapy concomitant with
a subcutaneous vaccine composed by allogeneic tumor extracts and liposomes with plasmids bearing IL-2
and GM-CSF genes. The treatment was safe: the only side effects were from mild to moderate and
manageable: pyrexia, swelling of the injected tumor and partial hair loss (alopecia). Due to disease
progression both patients were withdrawn from the study before completing the complete series of
interventions. These preliminary data encourage the completion of further clinical trials to establish the
possible clinical benefit of the proposed approach.}