Enhancing the therapeutic potential of oncolytic virotherapy for melanoma treatment

Melanoma remains a globally relevant malignancy. Although various treatments have been developed over time, few are effective against rarer mutations. To address this unmet clinical need, oncolytic virotherapy is being explored as a promising alternative. This thesis focuses on oncolytic adenoviruses, aiming to improve their therapeutic efficacy. A physico-chemical characterization was conducted on one first-generation (reference), one second-generation and four third-generation adenoviral vectors, evaluating zeta potential (z-value) and particle size. A screening for expression of CAR and DSG-2 adenovirus receptors was performed in two melanoma cell lines, MUG-Mel1 and A375. Subsequently, cell viability assays were performed to test the cytotoxicity of the adenoviral vectors and the immune checkpoint inhibitors (ICIs) Pembrolizumab and Ipilimumab. A combinatorial screening combining adenoviral vectors with ICIs was also carried out. Results showed high DSG-2 expression in both cell lines. Adenoviral vectors alone caused a dose-dependent decrease in viability, whereas ICIs alone had minimal effect. Screening of combinatorial strategy showed significantly reduced cell viability, with slight differences between the various vectors, thus confirming the complementary effect of virotherapy and immunotherapy. However, combining both ICIs with the virus did not enhance the effects further.