Chemoprotection by Transfer of Resistance Genes

Dose-limiting toxicity of chemotherapeutic agents, i.e., myelosuppression, can limit their effectiveness. The transfer and expression of drug-resistance genes might decrease the risks associated with acute hematopoietic toxicity. Protection of hematopoietic stem/progenitor cells by transfer of drug-resistance genes provides the possibility of intensification or escalation of antitumor drug doses and consequently an improved therapeutic index. This chapter reviews drug-resistance gene transfer strategies for either myeloprotection or therapeutic gene selection. Selecting candidate drug-resistance gene(s), gene transfer methodology, evaluating the safety and the efficiency of the treatment strategy, relevant in vivo models, and oncoretroviral transduction of human hematopoietic stem/progenitor cells under clinically applicable conditions are described.