expressed in cancer cells, however a "bystander effect" on surrounding tumour cells has been described with several suicide gene systems. Suppression of angiogenesis Angiogenesis (blood vessel formation) is an essential part of the formation of large tumour masses. Angiogenesis can be inhibited by the expression of several genes, which can be delivered to cancer cells in viral vectors, resulting in suppression of angiogenesis, and oxygen starvation in the tumour. The infection of cells with viruses containing the genes for angiostatin and endostatin synthesis inhibited tumour growth in mice. Enhanced antitumour activities have been demonstrated in a recombinant vaccinia virus encoding anti-angiogenic therapeutic antibody and with an HSV1716 variant expressing an inhibitor of angiogenesis. Radioiodine Addition of the sodium-iodide symporter (NIS) gene to the viral genome causes infected tumour cells to express NIS and accumulate iodine. When combined with radioiodine therapy it allows local radiotherapy of the tumour, as used to treat thyroid cancer. The radioiodine can also be used to visualise viral replication within the body by the use of a gamma camera. This approach has been used successfully preclinically with adenovirus, measles virus and vaccinia virus. Approved therapeutic agents Talimogene laherparepvec (OncoVEX GM-CSF), aka T-vec, by Amgen, successfully completed phase III trials for advanced melanoma in March 2013. In October 2015, the US FDA approved T-VEC, with the brand name Imlygic, for the treatment of melanoma in patients with inoperable tumors. becoming the first approved oncolytic agent in the western world. It is based on herpes simplex virus (HSV-1). It has also been tested in a Phase I trial for pancreatic cancer and a Phase III trial in head and neck cancer together with cisplatin chemotherapy and radiotherapy. Teserpaturev (G47∆), aka Delytact by Daiichi Sankyo is a first oncolytic virus therapy approved by Japan Ministry of Health, Labour and Welfare (MHLW). Delytact is a genetically engineered oncolytic herpes simplex virus type 1 (HSV-1) approved for treatment of malignant glioma in Japan. Oncolytic viruses in conjunction with existing cancer therapies It is in conjunction with conventional cancer therapies that oncolytic viruses have often showed the most promise, since combined therapies operate synergistically with no apparent negative effects. Clinical trials Onyx-015 (dl1520) underwent trials in conjunction with chemotherapy before it was abandoned in the early 2000s. The combined treatment gave a greater response than either treatment alone, but the results were not entirely conclusive. Vaccinia virus GL-ONC1 was studied in a