Determining the factors affecting breast cancer infectivity by oncolytic adenovirus

Cancer is the second leading cause of death in the United States. Traditional treatments for cancer, such as radiation and chemotherapy, are frequently ineffective and are often associated with painful side effects that diminish the quality of life for patients. New strategies for the treatment of cancer are greatly needed. Oncolytic viruses represent a new class of anticancer agents with the potential to greatly improve cancer treatment.

Genetically modified adenoviruses – specifically, adenovirus serotype 5 (Ad5) – are commonly used to generate oncolytic viruses. These adenoviruses are replication-selective, meaning that they have been engineered to replicate only in cancer cells bearing certain mutations. For example, ONYX-015 is a mutant adenovirus designed to exploit the loss of functional p53, a loss common to many cancer cells, in order to selectively destroy malignant cells [1]. Although the use of oncolytic viruses holds great promise for cancer therapy, the success of this strategy depends on the ability of adenovirus to infect cancer cells. We are using a panel of 50 breast cancer cell lines to study Ad5 infectivity. Affymetrix array data and CGH data have been collected for all of these cell lines. We have found that the ability of Ad5 to infect these cell lines is highly variable. CAR and αv integrins are known to be required for Ad5 entry. However, the infectivity of the breast cancer cell lines does not correlate with CAR levels or αv integrin levels. For example, BT474 cells appear to have ample CAR expressed on the surface but are infected at very low rates. Alternatively, both HCC 2185 cells and MDA MB 435 cells express very little CAR on the surface but are highly infectible. We are currently investigating the possibility that other cellular factors are influencing the ability of Ad5 to infect breast cancer cells.