SELECTIVE ELIMINATION (PURGING) OF CONTAMINATING MALIGNANT-CELLS FROMHEMATOPOIETIC STEM-CELL AUTOGRAFTS USING RECOMBINANT ADENOVIRUS

In this work we have explored the use of adenoviral vectors for the pu rging of cancer cells from hematopoietic stem cell (HSC) autografts. W e showed that a recombinant adenovirus expressing the herpes simplex-1 thymidine kinase gene (AD-tk) plus ganciclovir (GCV) killed HELA cell s more effectively than did GCV alone. HELA cells were then mixed with human HSCs and exposed to AD-tk/GCV. AD-tk/GCV reduced the number of HELA colonies to 4% of control values, with no detectable reduction in the hematopoietic progenitor, colony forming unit-granulocyte/monocyt e (CFU-GM). Similar studies of the JB6 non-Hodgkins lymphoma cell line showed a reduction to 5% of controls; studies of MCF-7, a breast carc inoma cell line, showed a reduction to 30% of controls, with no CFU-CM toxicity. Thus, AD-tk mediated selective killing of contaminating tum or cells. We also evaluated a recombinant adenovirus encoding the tumo r suppressor gene p53 (AD-p53). AD-p53 was able to selectively kill al l three cell lines (reducing tumor colonies approximately 100-fold) wi thout any toxicity to CFU-GM. Although both AD-tk/GCV and AD-p53 were effective in these experiments,AD-p53 seemed to be more potent. Adenov iral vectors show promise for selectively targeting cancer cells that contaminate HSC autografts.