Safety and Efficacy of Suicide Gene Therapy with Adenosine Deaminase 5-Fluorocytosine Silmutaneously in in Vitro Cultures of Melanoma and Retinal Cell Lines

Abstract

Local treatment as a treatment modality is gaining increased general acceptance over time. Novel drugs and methodologies of local administration are being investigated in an effort to achieve disease local control. Suicide gene therapy is a method that has been investigated as a local treatment with simultaneously distant disease control. In our current experiment we purchased HTB-70 (melanoma cell line, derived from metastatic axillary node) and CRL-2302 (human retinal epithelium) were from ATCC LGC Standards and Ancotil®, 2.5 g/250 ml (1 g/00ml) (5-Flucytosine) MEDA; Pharmaceuticals Ltd. UK. Adenosine Cytosine Deaminase (Ad.CD) was also used in order to convert the pro-drug 5-Flucytosine to the active 5-Fluoracil. Three different concentrations of 5-Flucytosine (5-FC) were administered (0.2ml, 0.8ml and 1.2ml). At indicated time-points (4h, 8h and 24h) cell viability and apoptosis were measured. Our concept was to investigate whether suicide gene therapy with Ad. CD-5-FC could be used with safety and efficiency as a future local treatment for melanoma located in the eye cavity. Indeed, our results indicated that in every 5-FC administration had mild cytotoxicity for the retinal cells, while increased apoptosis was observed for the melanoma cell line.

Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G

“…According to the genome of the patients we have chemotherapy treatment, tyrosine kinase inhibitors and immunotherapy. Intratumoral chemotherapy and combination of this treatment modality have been investigated in the past twenty years both in animal models and patients [13,15,16,[30][31][32][33]. There are several issues to address before starting such a study.…”

Clinical Trials in Metastatic Uveal Melanoma: Current Status

“…One is a phase 2 trial for anti-PD-1 naïve patients to receive gene therapy with intralesional injection of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) with valacyclovir and stereotactic body radiation therapy followed by nivolumab administration on day 17 (NCT02831933). This therapeutic combination builds on the concept of "suicide gene therapy," where a therapeutic gene-encoding enzyme (ADV/HSV-tk) is capable of transforming a nontoxic prodrug (valacyclovir) into a cell toxin that enhances the cytotoxic effect within cancer cells and protects the healthy cells [23]. Another clinical trial using a modified virus is a phase 1 study of VSV-IFNbetaTYRP1 in patients with metastatic uveal or cutaneous melanoma (NCT03865212).…”