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NEW APPROACH TO TREATING LEUKEMIA/LYMPHOMA EARNS NCI'S WALDMANN BRISTOL-MYERS SQUIBB AWARD FOR ACHIEVEMENT IN CANCER RESEARCH

NEW APPROACH TO TREATING LEUKEMIA/LYMPHOMA EARNS NCI'S WALDMANN
 BRISTOL-MYERS SQUIBB AWARD FOR ACHIEVEMENT IN CANCER RESEARCH
 /ADVANCE/ NEW YORK, April 9 /PRNewswire/ -- Thomas A. Waldmann, M.D., of the National Institutes of Health (NIH) in Bethesda, Md., today received the 15th Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research. The annual prize, which consists of $50,000 and a silver medallion, was presented at a luncheon in New York.
 The award recognizes Waldmann for his pioneering studies of the immune system that have led to promising new ways to use monoclonal antibodies to treat leukemias, lymphomas, and autoimmune diseases, and to prevent organ and bone marrow transplant rejection. Waldmann, chief of the Metabolism Branch of the National Cancer Institute (NCI), was selected for the award by an independent panel of leading cancer researchers.
 NCI Director Dr. Samuel Broder, who nominated Waldmann, described him as "a brilliant scientist who is internationally known for the major role he has played in bridging the gap between molecular biology and the patient." This opinion is echoed by 1991 Nobel Laureate Dr. E. Donnall Thomas, who called Waldmann "an outstanding clinician/scientist."
 During his 35-year career, Waldmann has made many important contributions to understanding the immune system. His landmark discovery in the 1970s that immune responses can be actively suppressed by certain immune cells revolutionized the way people think about the causes of immune diseases.
 "One of Waldmann's most crucial contributions has been his recognition that the receptor for the IL-2 growth factor that controls the growth and differentiation of immune system T-cells can be used for treatment of a variety of immune diseases," said Broder.
 This insight has led to a promising new treatment, currently in clinical trials, for the universally and speedily fatal adult T-cell leukemia, which is associated with HTLV-1. Of particular importance in these trials is Waldmann's ability to extend the survival of patients with adult T-cell leukemia. Patients with a life expectancy of no more than 20 weeks have, in some instances, been able to survive more than two years.
 Immune system cells, called T-cells, recognize specific invaders such as viruses or grafts through cell surface molecules called T- cell receptors. Waldmann observed that normal resting T-cells do not display receptors for interleukin-2 (IL-2), the protein that the cells need to grow. This is unlike activated T-cells found in certain leukemias and lymphomas and on T-cells of patients with auto immune diseases or organ transplants.
 Improved Monoclonal Antibodies
 Waldmann reasoned that a monoclonal antibody (Mab) could be used to disable the IL-2 receptor of leukemia cells and T-cells of other diseases. Mabs are laboratory-produced versions of antibodies the body produces to fight off foreign invaders. Without a functioning receptor, the cell would be deprived of the protein necessary to survive and grow.
 Moving the process from the laboratory to the patient, he prepared a Mab called anti-Tac (T-cell activated) that homes in on the activated T-cell and blocks the IL-2 from binding with its receptor, thus starving the cell. The first anti-Tac Mabs Waldmann prepared were from mice. However, there were a number of problems. Not only did the Mabs lack adequate killing power, they were destroyed by the patient's immune response to them. "They acted like guided missiles without a payload," said Waldmann.
 In a major achievement, Waldmann used genetic engineering techniques to substitute human components for mouse components in the anti-Tac Mab in order to counter the immune response to the antibody. While these humanized Mabs were less likely to be rejected by the immune system, they still lacked adequate killing power.
 To overcome this problem, he used the Mabs as messengers to deliver a modified toxin, developed by Dr. Ira Pastan of the NCI, directly to cancer cell receptors. More recently Waldmann has armed the Mabs with radioactive isotopes to deliver lethal blows to leukemia cells while leaving the normal cells unscathed. "This should add significantly to their effectiveness, especially in a disease like cancer, where it is essential that you kill every malignant cell," said Waldmann.
 Waldmann has received government permission to use these latest Mabs in human trials. However, he said: "In the long run I believe there is a realistic chance of success without added toxicity by using humanized antibodies without isotopes or toxins. I see these Mabs as playing a much greater role, especially for immune diseases other than cancer -- such as for treatment of autoimmune and graft versus host diseases and for the prevention of allograft rejection."
 According to Waldmann, these clinical applications provide a rational new approach to the treatment of certain cancers and autoimmune disorders and for the prevention of graft rejection. In the latter two situations, it is the attack of the immune system cells on the patient's own tissues or the graft that is responsible for the problem.
 Early Research
 Early in his career, Waldmann studied how antibodies survived, were broken down and transported in the body. This early research is still having an impact on the rational use of monoclonal antibodies. In the 1960s, before the advent of AIDS, he began to study how the immune system is normally regulated and what goes wrong in cancer and genetic immune deficiency diseases. Waldmann later applied the study of gene rearrangements to human leukemias and lymphomas to provide new methods for diagnosis and for monitoring the effectiveness of therapy.
 It is clear, as Broder has said, that while many people have made major contributions in either the basic sciences or clinical research, "it is orders of magnitude more rare to find someone who has been brilliantly successful in bridging the gap between these two disciplines, in a way that has earned Dr. Waldmann the highest respect and esteem of both pure basic scientists and pure clinicians."
 Waldmann received his M.D. degree from Harvard University in 1955 and was appointed house officer at Massachusetts General Hospital. He joined NIH in 1956 and became chief of the Metabolism Branch of NCI in 1971. In 1985 he was elected to the National Academy of Sciences and to the American Academy of Arts and Sciences in 1989. Among his other honors are invitations to present over 50 named honorary lectureships, and he has received the Milken Family Medical Foundation Award, the Stratton Medal and the Lila Gruber Cancer Research Award, among others.
 Waldmann is author or co-author of more than 500 scientific papers. His influence on other scientists is shown by the fact that he is listed as one of the 50 most-frequently cited scientific authors. Waldmann is also an accomplished amateur photographer. He was president of the NIH camera club where he was frequently named Photographer of the Year.
 Since 1977, the Bristol-Myers Squibb cancer grants program has provided no-strings-attached funding through 31 grants to 28 cancer centers in the United States and abroad in support of innovative, unrestricted basic or clinical cancer research. Totaling $15.34 million to date, the grants represent the largest unrestricted contribution made by a corporation in support of cancer research.
 The Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research is an annual prize to a scientist who has made a unique contribution to fundamental or clinical cancer research. Waldmann was selected by an independent peer-review committee chaired by Dr. Alan Sartorelli of Yale University. Members of the award selection committee represent institutions in the United States, Sweden and Japan that participate in the no-strings-attached cancer research grants program.
 Bristol-Myers Squibb initiated this program in 1977 and has since supported research in cancer, the neurosciences, infectious disease, nutrition orthopedics, pain and cardiovascular diseases, having provided more than $36 million in funds to date.
 Bristol-Myers Squibb is a research-based, diversified health care company whose principal businesses are pharmaceuticals, consumer products, nutritionals and medical devices.
 -0- 4/9/92/1100
 /CONTACT: Nancy Goldfarb of Bristol-Myers Squibb Company, 212-546-5107, or Virginia Mintz of Ketchum Public Relations, 202-835-8852, for Bristol-Myers Squibb Company/
 (BMY) CO: Bristol-Myers Squibb Company ST: New York IN: MTC SU:


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