Abstract
Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment. As metastatic cancers often become vigorously resistant to treatments, the development of novel, more potent and selective anti-cancer strategies is of great importance. Adenovirus (Ad) is the most commonly used virus in cancer clinical trials, however, regardless of the nature of the Ad-based therapeutic, complete responses to treatment remain rare. A number of pre-clinical studies have shown that, for all vector systems, viral spread throughout the tumor mass can be a major limiting factor for complete tumor elimination. By expressing exogenous cell-fusion proteins, many groups have shown improved spread of Ad-based vectors. This review summarizes the research done to examine the potency of Ad vectors expressing fusogenic proteins as anti-cancer therapeutics.
Highlights
Cancer is the second leading cause of death in high income countries, and the third leading cause of death in low and middle income countries, behind heart disease and infection [1]
In 2007, Hoffman et al examined the therapeutic efficacy of Ad vectors expressing the respiratory syncytial virus (RSV) fusion peptide RSV-F or vesicular stomatitis virus (VSV) fusion peptide VSV-G [77,78]
U87 tumor cells were infected with Ad-green fluorescent protein (AdGFP) and Ad5 wild-type (WT), and subsequently transfected with a plasmid expressing Gibbon ape leukemia virus (GaLV) fusogenic membrane glycoprotein (FMG). When these cells were co-cultured with mouse B16 cells, which lack the PiT-1 receptor for GaLV, AdGFP spread to the B16 cells at a higher frequency relative to un-transfected cells, suggesting a fusion-independent increase in viral spread induced by enhanced release of the virus in the FMG-expressing cells
Summary
Cancer is the second leading cause of death in high income countries, and the third leading cause of death in low and middle income countries, behind heart disease and infection [1]. Adenovirus efficiently infects a wide variety of human cell types, regardless of cell cycle status, and has a relatively large cloning capacity [8] These desirable qualities have led to a vast amount of research into their use as oncolytic vectors or as delivery vehicles for anti-cancer therapeutic genes. An encouraging approach under investigation to enhance viral spread through a tumor involves heterologous expression of fusion-inducing fusion‐inducing proteins from the therapeutic vector. This approach has shown promise in increasing viral spread throughout the tumor mass, and in facilitating activation of review, wewe will discuss recent studies in the activation of the thehost hostanti-tumor anti‐tumorimmune immuneresponse.
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