Oncorine (H101), an oncolytic adenovirus, to be used in combination with chemotherapy as a treatment for patients with late stage refractory nasopharyngeal cancer. This marks the first oncolytic viral therapy approved by any regulatory agency in the world and this is the second commercial gene therapy product. H101 is essentially a modified version of Onyx-015, initially developed by Onyx Pharmaceuticals. Besides Oncorine, Shanghai Sunway Biotech develops a tumor-targeted recombinant adenovirus injection (H102) and an oncolytic recombinant adenovirus injection (H103) for treatment of cancer. H102 specifically targets primary hepatocellular carcinoma. H103 adenoviruses lyses the tumor cells and expresses Hsp70 that can potently stimulate an antitumor immune response.
Hospital list that offer therapy:
Process of Therapy:
Introduction of oncorine
Oncorine (Recombinant Human Adenovirus Type 5 Injection) is the first oncolytic virus drug which was approved in the world and independent intellectual property is hold by the company. After oncorine was listed on national 863 plan and SME Innovation Foundation of Science and Technology Ministry in 2000, it had been listed on “the 10th five-year plan” of major science and technology projects for national “863” plan in 2002. It was adopted as project of Shanghai New and High-tech Achievements Transformation in 2004. Oncorine was got NDA of national calss I biological products in October, 2005. Offical formal manufacture approval was got in April, 2006. And it was successful on the market since September in the same year.
1.Construction of Oncorine
The virus is reconstructed with deleting E1B-55KD and E3 region of wild adenovirus type 5. The black parts are deleted as following.
2.MOA of Oncorine®
Selective theory depending on the status of P53
In normal cells, early proteins (E1A and E1B) are expressed when they are infected by adenovirus. And early proteins are related with virus replication. The cell response for expression of E1A protein is to stimulate P53 expression. P53 is an important transcription regulation factor and a product of tumor suppressor gene. P53 overexpression results three changes in the cell: 1) cell arresting 2) DNA damage-repair 3) Inducing apoptosis. Those reations are preventing replication of viruse in normal cells. E1B-55KD can degrade P53 protein , which favoring to virus replication. Comparing with wild virus, replication abilityof E1B-55KD deleted virus was reduced; meanwhile, P53 couldn’t be degraded effectively when E1B-55KD is deleted. So that oncorine® can’t replicated in normal cells. In P53 deficient cancer cells , reactions of cells’ can not be induced because of P53 deficiency, it is conducive for replication of reconstructed virus. The current view is that it is not only P53 mutation itself, but also P53 pathway deficiency are conducive for selective replication of oncorine®.