Stammzellen als zelluläre Vehikel virotherapeutischer Agenzien beim metastasierten Mammakarzinom

Abstract

Despite advances in therapy, metastatic breast carcinoma maintains a disappointing 5-year survival rate of 20.4 %. Hence, there is a need for alternative and complementary therapeutic strategies. In this regard oncolytic virotherapy is a promising approach that uses mainly conditionally replicative viruses (CRAds) to selectively kill tumor cells by exploiting the lytic property of virus replication. Adenovirus-based vectors have emerged as leading candidates for in vivo virotherapy. However intravenously injected CRAds have shown only limited antitumor efficacy due mainly to low viral infectivity and insufficient viral delivery to the sites of tumor. Based on recent findings that systemically administered human mesenchymal stem cells (hMSCs) home to breast cancer metastasis of the lung, our investigation assesses the possibility of using hMSCs as cellular virus carriers to pulmonary metastases of breast cancer. HMSCs were transduced with CRAds. In a SCID mouse xenograft model we established breast cancer pulmonary metastatic disease to examine the effects of intravenously injected CRAd-loaded hMSCs versus CRAds alone. In mice treated with CRAd-loaded hMSCs the transduced stem cells homed to the metastatic lesions and led to reduced tumorgrowth and extended survival compared to mice treated with CRAds alone. We concluded that systemically administered hMSCs transduced with CRAds have the ability to home in on and kill metastatic breast cancer cells; these findings validate the feasibility of using hMSCs as cellular vehicles for the targeted therapy of metastatic breast cancer with CRAds.