The FASEB Journal, Vol 11, 640-648, Copyright © 1997 by The Federation of American Societies for Experimental Biology

REVIEWS

Hematological malignancies

MK Brenner
Cell and Gene Therapy Program, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

The present cure rate for leukemia and lymphoma represents one of the success stories of modern cancer therapy. However, treatments remain toxic, expensive, and ineffective for many patients. There is therefore considerable interest in exploring gene therapies for these disorders. To date, four major strategies have been adopted: 1) modifying the tumor cell itself either by "repairing" one or more genetic defect associated with the malignant process, introducing a gene that will trigger an anti-tumor immune response, or delivering a pro-drug metabolizing enzyme that will render the tumor sensitive to the corresponding cytotoxic agent; 2) modifying the immune response to the tumor by altering the specificity or effector function of immune system cells; 3) decreasing the sensitivity of normal host tissue by delivering cytotoxic drug resistance genes to marrow precursor cells and thereby increasing the therapeutic index of cytotoxic agents; and 4) marking normal and malignant hemopoietic cells in order to more closely monitor the efficacy of conventional therapies. Given the current "state of the art," all these approaches have significant limitations, but each has had its successes, offering encouragement for future applications in clinical practice.

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