VV has been engineered to express adipokine leptin to reprogram tumor-infiltrating T cell metabolism through the persistence of mitochondrial function and a higher OXPHOS in activated CD8+ T cells, resulting in active immune responses and promotion of memory responses to secondary tumor challenge in melanoma-bearing mice.260 Recombinant OVs that express other metabolic modulating proteins, such as insulin or IGF-1, have also been patented and investigated for their role in promoting metabolic reprogramming and immune effects of T cells (WO2019148109). This evidence concerns the gene CD8A and melanoma.