293 Cells adenovirus vector replication

Fallaux FJ, Bout A, van der Wollenberg DJ, Hehir KM, Keegan J, Auger C, Cramer SJ, van Ormondt H, van der Eb AJ, Valerio D, Hoeben RC (1998), New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses, Hum. Gene Ther. 9 1909-1917. 

Oncolytic Adenoviruses. A class of AdVs has been developed to specifically kill cancer cells, an approach that has been termed virotherapy [56]. Contrary to the approach pursuedi with first-, second-, and third-generation adenovirus vectors, these oncolytic or conditionally replicating adenoviruses (CRAds) are engineered in such a way that they retain the ability to replicate. This replication however, is tumor selective—the virus will only infect and proli-ferate in malignant cells with mutations in specific tumor suppressor genes [2, 19, 56]. Thus, a transgene is actually not required for the therapeutic effect to take place. 

Adeno-associated viruses are naturally defective viruses that require a helper adenovirus to replicate normally. However, they are capable of infecting a range of cells and can integrate at specific sites in human chromatin. Adeno-associated viruses have been used experimentally to kill certain forms of breast, cervical, and prostate cancer cells. As viral vectors, they have been used to introduce a gene for production of insulin and the genes for both Factor VIII and Factor IX, lacking in humans with certain forms of hemophilia (hemophilia A and B, respectively). 

Gao GP, Engdahl RK, Wilson JM. A cell line for high-yield production of El -deleted adenovirus vectors without the emergence of replication-competent virus. Hum Gene Ther 2000 11 213-219. 

The ongoing clinical trials include the use of adenovirus and herpes virus vectors. One example of adenoviral vector is ONYX-015, which lacks E1B protein, required for replication with a normal p53 pathway and RNA export during viral replication. It has been used to treat squamous cell carcinoma of the head and neck and has also been tested as a preventive treatment for oral precancerous tissue. The concept behind using this vector is that ONYX-015 will proliferate in p53 pathway-deficient tumor cells and kill them. 

The oncolytic viruses include adenovirus, measles, reovirus, vesicular stomatitis virus (VSV),HSV,poxvirus, and vaccinia. Specific examples include (1) ONYX-015, which is an adenoviral oncolytic virus, administered to patients with liver metastases of colorectal cancer and pancreatic cancer [29], (2) Reolysin, which is an oncolytic reovirus administered to patients with glioma [30], and (3) MV-CEA, which is an oncolytic measles virus expressing carcinoembryonic antigen, administered to patients with ovarian cancer [31]. Some oncolytic viruses are wild type and are apparently not pathogenic in humans, such as the Newcastle disease virus (NDV), which is an RNA avian paramyxovirus. PV701, a naturally attenuated, replication-competent strain of NDV, has been administered to patients with advanced solid tumors [32], The applicability of oncolytic viruses as a therapy for clinical oncology trials is due to their potential selectivity the ability to kill tumor cells but not normal cells. However, the level of attenuation of viral replication in normal cells is limited for most oncolytic vectors. 

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