Use of Reovirus as an Anti-Breast Cancer Agent

摘要

We previously demonstrated that the human reovirus preferentially infects cancer cells with an activated Ras signalling pathway. In this study, we investigated the feasibility of reovirus as a therapeutic against breast cancer. We examined a panel of breast cancer cell lines as well as a non-tumorigenic epithelial cell line derived from normal tissue for in vitro reovirus replication. All five of the tumor-derived cell lines were efficiently lysed by the virus, while the non-transformed cells were resistant to infection. One of the cell lines, MDA-MB-4358, was implanted in the mammary fat pad of SCID mice as xenografts, which were subsequently injected with reovirus. Tumor regression was found to be rapid and complete. Furthermore, in a bilateral tumor SCID mouse model, a single unilaterally injection with reovirus resulted in dramatic regression of the tumor size in both the injected and remote tumors, raising the therapeutic possibility of systemic delivery of reovirus. Finally, the ability of reovirus to act against primary breast cancer tumors was determined ex vivo; we found that reovirus could effectively replicate in primary human breast tumor specimens.