Applications of gene transfer in hematologic malignancy.

Abstract

Although gene transfer was originally conceived as a means to replace or correct defective genes in patients with inherited disorders, the process has shown broad potential for intervention in hematologic malignancy and for study of hematopoietic stem cell biology. Gene transfer strategies now under investigation for these applications include 1) repair of one or more genetic defects associated with the malignant process, 2) delivery of a prodrug-metabolizing enzyme that causes tumor cells to become sensitive to the corresponding anticancer drug, 3) modification of immune responses to the cancer, and 4) introduction of drug resistance genes to increase the therapeutic index of cytotoxic agents. Finally, by marking normal or malignant cells with readily detectable genes, one can monitor the efficacy of therapy or study the dynamics of stem cell behavior in vivo. At present these applications are limited by the quality of vectors, but as transduction efficiencies and gene regulatory mechanisms improve, gene transfer can be expected to evolve into a major therapeutic modality in its own right.