Chemoresistance gene transfer into hematopoietic cells: hope and pitfalls

Our better understanding of chemotherapy resistance has led to the proposal that gene therapy can protect hematopoietic stem cells from cytotoxic drug s toxicity. Transfer of drug resistance genes;into hematopoietic cells may allow the administration of higher doses of chemotherapy and, thus, increas e regression or even cure for chemosensitive tumors. In addition, chemoresi stance genes: can be used to allow in viva selection of transduced cells af ter the administration of cytotoxic drugs. Preclinical studies using MDR1.( multidrug resistance 1), mDHFR (mutants of dihydrofolate reductase) and MGM T (methylguanine DNA methyltransferase) genes have already proven the feasi bility this approach. Our group has studied the potential value of MRP (mul tidrug resistance-associated protein) to protect hematopoietic cells. Phase I clinical trials are currently in progress. However the ::low stem-cell t ransduction efficiency limits the clinical:applications.