Awarded: Jan 01, 1999
$12.55 million over 5 years
In 1999, four outstanding physician-scientists at the mid-career level each received grants of $600,000 per year for 5 years.
1999 DCSA Grantees
Kenneth C. Anderson, M.D.
Dana-Farber Cancer Institute
"Development of Novel Treatment Approaches for Multiple Myeloma"
Alan M. Gewirtz, M.D.
University of Pennsylvania School of Medicine
"Nucleic Acid Therapeutics for Human Leukemia"
David A. Scheinberg, M.D., Ph.D
Memorial Sloan-Kettering Cancer Center
"Specific Immunotherapy of Cancer: Targeting Therapy Selectively to the Neoplastic Cell"
Bruce D. Walker, M.D.
Harvard Medical School
Massachusetts General Hospital
"Immune Reconstitution in HIV Infection"
Kenneth C. Anderson, M.D.
Dana-Farber Cancer Institute
"Development of Novel Treatment Approaches for Multiple Myeloma"
Dr. Anderson is an independent investigator in the Hematologic Malignancies Disease Center at Dana-Farber Cancer Institute and an Associate Professor of Medicine at Harvard Medical School. His research interests include cellular and molecular mechanisms regulating myeloma cell growth and survival and novel immune-based therapies for myeloma.
In 1997, Dr. Anderson hosted the VI International Workshop on Multiple Myeloma in Boston. He serves on the Board of Directors and Board of Scientific Advisors of the International Myeloma Foundation and is Chairman of the Board of Scientific Advisors of the Multiple Myeloma Research Foundation.
Dr. Anderson graduated from Johns Hopkins Medical School in 1977 and trained in internal medicine at Johns Hopkins Hospital. He completed his training in hematology, medical oncology, and tumor immunology at the Dana-Farber Cancer Institute.
Abstract:
Development of Novel Treatment Approaches for Multiple Myeloma
Development of Novel Treatment Approaches for Multiple Myeloma. Multiple myeloma is a presently incurable bone marrow cancer which will affect 13,700 new individuals in the U.S. in 1999 and account for 2% of cancer-related deaths. Dr. Anderson has assembled a team of basic and clinical researchers to develop new biologically-based treatment strategies for myeloma. These therapies target not only the tumor cell, but also its bone marrow microenvironment, in order to achieve more complete and selective eradication of myeloma cells, improved disease-free survival for patients, and ultimate cure. Laboratory studies will define factors in the tumor cell itself and its microenvironment, such as increased formation of new blood vessels, which permit myeloma cells to grow and survive in the bone marrow. Basic studies will provide the rationale for novel treatments to selectively inhibit tumor growth, induce tumor cell death, and overcome the ability of tumor cells to resist currently available conventional treatments. Simultaneously, the team will develop methods for enhancing immune responses against myeloma cells in the laboratory. These studies will provide the basis for vaccination treatments to specifically target myeloma cells. The team will also identify and characterize those cells in the immune system which are capable of recognizing and killing myeloma cells. These cells will be expanded in the laboratory and then transfused to patients to provide an alternative form of anti-myeloma therapy.
Alan M. Gewirtz, M.D.
University of Pennsylvania School of Medicine
"Nucleic Acid Therapeutics for Human Leukemia"
Dr. Gewirtz is Professor of Medicine and Pathology at the University of Pennsylvania School of Medicine and Leader of the Stem Cell Biology and Therapeutics Program in the Cancer Center. He has devoted his career to studies of normal and malignant human hematopoiesis and ways of translating basic scientific discoveries into clinically useful therapies for patients with disorders of blood formation.
A member of the NIH Experimental Therapeutics Study Section and the Hematology Study Section of the Veterans Administration, Dr. Gewirtz serves on a number of editorial boards and reviews manuscripts for numerous scientific journals. He is also a member of the Medical/Scientific Advisory Committee of the Leukemia Society of America and is a National Trustee of the organization. He was elected to the American Society of Clinical Investigation in 1990.
Dr. Gewirtz received his M.D. and M.A. in microbiology from the State University of New York at Buffalo, which he attended from 1971-76. He completed training in internal medicine at Mt. Sinai Hospital in New York and in hematology and oncology at Yale University. After completing clinical and research fellowships at Yale, Dr. Gewirtz was on the faculty of Temple University School of Medicine from 1984-90.
Abstract:
Nucleic Acid Therapeutics for Human Leukemia
Nucleic Acid Therapeutics for Human Leukemia. The overall goal of this project is to advance the development of more effective, and less toxic, therapies for human leukemia. The principles learned will hopefully be applicable to a larger spectrum of blood disorders, and perhaps cancer and cardiovascular diseases as well. To accomplish this goal, the program will focus on the use of short strands of nucleic acids (oligonucleotides), the building blocks of all genetic information, to disrupt gene expression in diseased cells. Since a number of genes responsible for causing leukemia have been identified, "switching off" these genes with nucleic acid drugs should prove to be a highly effective therapeutic strategy. Such therapy should also prove much less toxic to the patient than chemotherapy and radiation, because it is highly specific for the leukemia cells. To switch off target genes, the flow of genetic instructions will be disrupted at the RNA level. RNA is the "blueprint" that a cell reads in order to construct the proteins it needs to live. These "blueprints" can be disabled or destroyed by oligonucleotides which bind directly to them, or which attract away proteins that protect the RNA. While often effective in the laboratory, the ability to employ nucleic acid-based therapies in the clinic remains theoretical and unproven.
The aims of the program will be to advance the use of oligonucleotide drugs in the clinic by:
- Developing a detailed understanding of how oligonucleotide molecules enter cells and interact with the RNA of targeted genes;
- Identifying advantageous RNA targets for oligonucleotides in leukemic cells; and
- Testing the potential utility of candidate oligonucleotides in relevant pre-clinical models.
The most promising oligonucleotides will then be used to initiate Phase I/II clinical studies in leukemic patients.
David A. Scheinberg, M.D., Ph.D
Memorial Sloan-Kettering Cancer Center
"Specific Immunotherapy of Cancer: Targeting Therapy Selectively to the Neoplastic Cell"
Dr. Scheinberg is Attending and Chief of the Leukemia Service at Memorial Hospital and Member and Head of the Hematopoietic Cancer Immunochemistry Laboratory at Sloan-Kettering Institute. His work is focused on the discovery of new cancer immunotherapies, such as monoclonal antibodies and vaccines, and the testing of them in clinical trials in patients with cancer. Dr. Scheinberg holds an appointment in the Department of Molecular Pharmacology and Therapeutics and Department of Medicine at Cornell Medical College and is an advisor to several charitable foundations and companies developing new strategies for treatment of patients with cancer. He is a former Scholar of the Lucille P. Markey Charitable Trust and a translational investigator of the Leukemia Society of America.
Dr. Scheinberg trained at the New York Hospital/Cornell University Medical Center in internal medicine and at Memorial Sloan-Kettering Cancer Center in medical oncology, before joining the staff at Sloan-Kettering in 1987. He received his M.D. and Ph.D. in pharmacology and experimental therapeutics from Johns Hopkins Medical School in 1983.
Abstract:
Specific Immunotherapy of Cancer: Targeting Therapy Selectively to the Neoplastic Cell
Specific Immunotherapy of Cancer: Targeting Therapy Selectively to the Neoplastic Cell. The program proposes to harness the immune system to specifically kill cancer cells while sparing normal cells and tissues. Two strategies will be employed. In the first, monoclonal antibodies (proteins of the immune system that can target cancer cells) will be used to deliver highly potent radioactive particles directly to cancer cells to kill them. These particles, known as alpha particles, are extraordinarily powerful, yet travel such short distances that they do not damage normal cells and tissues in the vicinity of the cancer. The second approach aims to develop vaccines that will stimulate the patient's immune system to recognize abnormal cancer-causing proteins found exclusively in the cancer cells. The aim is to have the cells of the immune system selectively attack and kill those cancer cells that have these proteins while sparing normal cells. At the current time, this program is the only one worldwide to use these two strategies in people.
Bruce D. Walker, M.D.
Harvard Medical School
Massachusetts General Hospital
"Immune Reconstitution in HIV Infection"
Dr. Walker is Director of the Partners AIDS Research Center at Massachusetts General Hospital and Brigham and Women's Hospital, and an Associate Professor of Medicine at Harvard Medical School. His work focuses on efforts to boost immunity in HIV-1 infected people in order to gain immunologic containment of the virus.
Dr. Walker's contributions include the identification of a strong cytotoxic T cell response to HIV in infected people; the identification of an association between strong HIV-1-specific T helper cell responses and control of viremia; and the demonstration of an association between strong T helper cell responses and strong CTL responses in people who are able to control viremia without drug therapy.
Dr. Walker graduated from Case Western University School of Medicine in 1980. Following an internship and residency at Massachusetts General Hospital and Harvard Medical School, he completed a postdoctoral fellowship in the laboratory of Robert T. Schooley, studying the cellular response to HIV in infected people.
Abstract:
Immune Reconstitution in HIV Infection
Immune Reconstitution in HIV Infection. This project is based on the hypothesis that the body's natural defense mechanisms can effectively control the AIDS virus. It is based on the identification of people infected with HIV for over 20 years, who have never been treated with antiviral drugs and yet continue to be entirely well. Dr. Walker and his colleagues have already identified key components of natural defense mechanisms in these people, which work together to destroy HIV-infected cells. These include both killer cells (also called cytotoxic T cells) that kill virus-infected cells before new viruses can be produced, and helper cells that help killer cells to function efficiently. In addition, the team has shown that treatment of HIV-infected people in the earliest stages of infection leads to generation of potent helper and killer cells. The specific aims of the project focus on the establishment of a Center for HIV-1 Immunotherapy, which will provide a stable infrastructure to fuel basic science research and allow them to perform cutting-edge clinical trials to increase natural defense mechanisms against HIV. A leading program for basic science research related to HIV-1 immunology has been established, and funding from this award will expand the effort to define precisely the correlates of immune protection. Furthermore, the researchers will translate promising research findings into clinical trials to augment HIV-1-specific immunity to the benefit of infected patients.