Gene Therapy of Breast Cancer: Studies of Selection Promoter/Enhancer-Modified Vectors to Deliver Suicide Genes.
Annual rept. 1 Sep 95-31 Aug 96,
DANA-FARBER CANCER INST BOSTON MA
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Tumor contamination of bone marrow BM and peripheral blood PB may affect the outcome of patients receiving high dose chemotherapy with autologous transplantation of hematopoietic stem cell products. We demonstrate that replication defective adenoviral vectors containing DF3MUC1 carcinoma-selective promoter can be used to selectively transduce contaminating carcinoma cells. Adenoviral-mediated reporter gene expression in breast cancer cells was 5-6 orders of magnitude higher than that found in BM, PB and CD34 cells and can detect one breast cancer cell in 5 x 10exp 5 BM or PB cells with a vector containing the DF3MUC1 promoter. We also show that transduction of the HSV-tk gene for selective killing by ganciclovir GCV can be exploited for purging cancer cells. The selective expression of TK followed by GCV treatment resulted in the elimination of 6-logs of contaminating cancer cells. There was little effect on CFU-GM and BFU-E or LTCICs. These results indicate that adenoviral vectors with a tumor-selective promoter provide a highly efficient and effective approach for the detection and purging of carcinoma cells in hematopoietic stem cell preparations.
- Medicine and Medical Research