To address this problem, an attenuated vaccinia virus called modified vaccinia Ankara (MVA) was developed for high- risk individuals. MVA was generated by over 500 serial passages of a smallpox vaccine from Ankara, Turkey, in chicken embryo fibroblasts, resulting in over 15% loss of the vaccinia virus genome. 25 MVA can infect mammalian cells and express transgenes, but it cannot produce infective viral particles. Bavarian Nordic has further generated a proprietary isolate of MVA designated MVA -BN. MVA- BN exhibits a severely restricted host range and fails to replicate in most mammalian cells , including primary human cells and most transformed cell li nes. 1.2.13 Clinical Experience with MVA Vector -Based Trials Several clinical trials in metastatic renal cell carcinoma have been conducted with the TroVax vaccine, which consists of a recombinant MVA expressing the 5T4 TAA. Initial trials demonstrated some obje ctive clinical responses, stable disease, and both antibody and T- cell responses to 5T4. A phase III randomized, placebo-controlled study employed MVA 5T4 with and without cytokines and sunitinib in patients (n = 733) with metastatic renal cell cancer (Tab le 5). Treatm ent arms were well -balanced.