Targeting a Novel Vector for Breast Cancer Gene Therapy
Annual rept. 15 Jul 2000-14 Jul 2001
DARTMOUTH COLL HANOVER NH
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We are testing the hypothesis that a model parasite gene therapy vector can be genetically altered to safely, specifically and effectively target breast cancer cells in vitro and in vivo. We have developed a novel strategy to establish the protozoan parasite T. gondii as the next generation vector for breast cancer gene therapy. The significant innovative aspect of this approach is the promise of this strategy to deliver a novel vector for breast cancer gene therapy that is potentially superior to the current vectors under current development and refinement. The primary purpose and scope of this IDEA award project is to experimentally examine approaches to safely target the Toxoplasma gondii parasite gene therapy vector to breast cancer tissue using in vitro and in vivo models. In this reporting period we have found that the cytosine deaminase CD and thymidine kinase TK markers expressed in T gondii produce a bystander killing effect on both human fibroblasts and SKBR3 tumor cells in vitro. We also report construction of a highly attenuated uracil auxotrophic T gondii parasite strain for safely targeting gene therapy to breast cancer. Using trifunctional ezyme expression plasmids we have co-expressed both the TK and CD markers in transgenic T gondii. We are examining the expression of HSV TK and bacterial CD in attenuated T gondii, response to ganciclovir and 5-fluorocytosine, as well as methods for targeting this vector to breast cancer cells overexpressing HER2neu. High affinity antibodies to examine a bi-specific targeting approach have been obtained.
- Medicine and Medical Research