Ribozyme-Mediated Breast Cancer Gene Therapy

In our laboratory we have developed lentiviral vectors for use in anti-breast cancer gene therapy. Our specific goal for this project was to evaluate the feasibility of using lentiviral vectors that express anti-HER-2/neu antisense or ribozymes for the treatment of breast cancer. The advantage of le...

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Bibliographic Details
Main Authors: Pitha-Rowe, Paula M, Dropulic, Lesia, Dropulic, Boro
Format: Report
Language:English
Subjects:
ANTISENSE
BREAST CANCER
CELLS(BIOLOGY)
DISEASE VECTORS
GENE THERAPY
Genetic Engineering and Molecular Biology
HER-2
LENTIVIRAL VECTORS
Medicine and Medical Research
RETROVIRUSES
RIBOZYMES
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Summary:In our laboratory we have developed lentiviral vectors for use in anti-breast cancer gene therapy. Our specific goal for this project was to evaluate the feasibility of using lentiviral vectors that express anti-HER-2/neu antisense or ribozymes for the treatment of breast cancer. The advantage of lentiviral vectors over other vectors is that lentiviral vectors can transduce human cells with great efficiency. We have demonstrated that HIV- based lentiviral vectors can transduce a variety of human cell types with up to 99% efficiency, as measured by FACS analysis of GFP expression. Specifically, these vectors can transduce human breast cancer cells with up to 90 to 97% efficiency. HER-2 overexpressing breast cancer cell lines, transduced with a lentiviral vector that expresses an anti-HER-2 antisense sequence, exhibit slower growth in vitro compared to non-transduced cells. In addition, breast cancer tumors in nude mice, formed by injection of breast cancer cells transduced with the anti-HER-2 lentiviral vector, tended to grow more slowly than tumors formed by non-transduced breast cancer cells. Modifications and improvements of the current vector system can potentially generate a potent genetic therapy for breast cancer. Original contains color plates: All DTIC reproductions will be in black and white.