Endothelial Progenitors as Vectors for Systemic Gene Therapy of Breast Cancer
Final rept. 10 Jul 2000-9 Jul 2004
ALABAMA UNIV IN BIRMINGHAM
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14. ABSTRACT Gene therapy offers a potentially important treatment for breast cancer, however a noted problem with current vector systems is the lack of efficient and targeted systemic delivery to the primary tumor and disseminated metastases. To address this issue we proposed the use of endothelial progenitor cells EPCs, which have the propensity of homing to sites of neovascularization characteristic of growing tumors. The success of this approach requires efficient isolation of EPCs and subsequent loading of the EPCs with therapeutic modalities. We hypothesized that EPCs can, after intravascular injection, localize into sites of tumor neovascularization and deliver therapeutic payloads. In this regard, the key findings of this research project are that 1 EPCs can be isolated and enriched from fresh human blood, 2 blood-isolated EPCs can be efficiently loaded with therapeutic adenovirus Ad vectors, 4 the oncolytic Ad vectors are able to amplify their therapeutic payloads within the EPCs, 5 loading EPCs with Ad vectors does not inhibit their intrinsic homing activity, and 6 loaded EPCs deliver the oncolytic Ad vectors that exert an effective anti-tumor activity. Overall, the findings of this project support the application of therapeutic EPCs as cellular vehicles for gene therapy of both local and disseminated breast cancer.
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