Over the Rooftops of Time: Jewish Stories, Essays, Poems

Human Gene Therapy

Human Gene Therapy Harnessing the Body’s Defenses Against Cancer Scientists, like Talmudic scholars, work along a continuum— some researching the minute particulars of an issue, others looking at whole structures. The Talmudist might ask: How shall we know which prayers to recite during the three watches of the night? By what signals shall we determine when the watch has concluded and a new one begun? And what guide shall inform us of the arrival of morning? Some say, when you can tell the difference between a white thread and a blue. Or when you can distinguish between a wolf and a dog. Others in this tradition engage in debate over more comprehensive issues and devote their lives to considering major ethical or legal systems. Dr. Steven Rosenberg, chief of surgery at the National Cancer Institute, belongs in this second category, attempting to address the way the body itself reveals its own strategies for maintaining its integrity and health and provides a complex surveillance system to do so. By harnessing the body’s own defense 1 0 9 system, augmenting it, amplifying the body’s ability to recognize foreign cells and deal appropriately with them, rather than seeking to use agents external to the body, Rosenberg takes part in a new chapter in biologic therapies and cancer treatment. Chemotherapy, radiation and surgery aim directly at the cancer. Biologic therapy assists the body in recognizing and responding to cancer-causing agents. CANCER INCIDENCE: Why be concerned with developing new weapons against cancer? Chemotherapy, surgery, and radiation have provided a fifty percent cure rate in terms of normal actuarial survival. Rosenberg is quick to point out that despite the improvement in survival, the incidence of cancer is staggering. In 1991 deaths from cancer in the United States numbered 515,000. Compared with 300,000, the total of all deaths in World War II: 57,000 deaths in Viet Nam: 18,000 deaths last year from AIDS, it would not seem that we have come very far in our efforts to slow down the effects of cancer. One out of four people now alive will develop invasive cancer. BIOLOGIC THERAPY—WHAT IS IT? In biologic therapy an attack is not mounted against the cancer directly as it is with chemotherapy, surgery, and radiation. The body recognizes some cancers as foreign but at times it is a weak recognition. Therefore the body’s defense against cancer must be altered. The host is assisted in its ability to fight by enlisting the cellular arm of the immune system. The question is, How can the body’s immune response be stimulated? There were known albeit rare instances of spontaneous regressions of cancers. Could these provide any clues to strategies for treatment? Twenty-three years ago Rosenberg, then in surgical training, treated such a patient who some twelve years earlier had been diagnosed with a metastatic, essentially untreatable stomach tumor. To Rosenberg’s surprise , the patient was alive and well all these years later. Could the use of this man’s cells shed any light on cancer treatment? Efforts to treat both humans and animals, including an attempt to grow a sarcoma nodule in the mesentery of miniature pigs and transfuse treated cells by IV back to a patient, were unsuccessful. One of the missing ingredients in those days was some way to grow lymphocytes outside of the body and to amplify them. Robert Gallo’s group at NIH provided the key through the isolation of a T-cell hormone , Interleukin-2. 1 1 0 OVER THE ROOFTOPS OF TIME THE ARSENAL: The body’s ability to react immunologically to tumor cells can be inhibited in at least two of the following ways: tumorkilling cells can have difficulty reading the tumor cells as foreign; if the recognition function does work effectively, the immunological response can sometimes mobilize not only the killer cells but also the suppressor cells whose function it is to regulate the immune response. Knowledge of four key substances produced by the body—interleukin -2 (IL-2), tumor-necrosing factor (TNF), lymphokine-activated killer cells (LAK), tumor infiltrating lymphocytes (TIL)—has opened the way to current research. IL-2, interleukin-2, is a T-lymphocyte growth factor that both increases the number of T-lymphocytes and activates certain T-cells to become cancer-killing cells called lymphokine-activated killer cells or LAK. These killer cells cause no harm in vitro to...