Marrow Protection: Transduction of Hematopoietic Cells with Drug Resistance Genes (Progress in Experimental Tumor Research, Vol. 36)

Successful transfer of drug resistance genes into hematopoietic stem cells affords promise as a means of protecting patients from the myelotoxicity of anti-cancer drugs and may permit dose intensification and better outcomes. The use of peripheral blood mobilized progenitor cells has improved the access to this cell population and ex vivo gene transfer approaches. Transfer of drug resistance genes into peripheral blood mobilized progenitor cells together with nonselectable genes, also offers the possibility of expression of proteins produced by these genes and correction of genetic deficiencies or expression of other desirable proteins such as antibodies. The studies published in this book review the progress in this field, emphasizing the work done with retroviral vectors and various genes that may be used to confer specific types of drug resistance to recipients. Authored by experts in the field, this volume provides a comprehensive review of the problems and opportunities in gene therapy focusing on the use of various drug resistance genes to provide protection of hematopoietic cells against drug toxicity. General topics include basic principles of gene transfer, optimizing conditions for gene transfer in hematopoietic cells, and gene transfer in the nonmyeloablated host. Specific chapters describe constructions and preclinical studies of specific genes that impart resistance to anticancer drugs when expressed in hematopoietic cells including MDR-1, mutated forms of human methylguanine-DNA-methyltranferase, mutant forms of dihydrofolate reductase and thymidylate synthase, dihydropyrimidine dehydrogenase and cytidine deaminase. For successful transfer of drug resistance genes, the possibility that they may be used as selectable markers and that marrow ablation may not be required are important considerations. This book is especially timely, as clinical trials with these drug resistance genes are expected to increase markedly in the next few years. It should appeal to all interested in stem cell biology and gene therapy, as well as clinicians who look forward to using this technology in their practice.