WHITE PLAINS, N.Y., Sept. 6, 2012 -- The Leukemia & Lymphoma Society (LLS) today announced it has awarded four new grants through its prestigious Marshall A. Lichtman Specialized Center of Research (SCOR) research initiative, bringing the program's total funding to $260 million since its inception in 2000.
All Principal Investigators have long-time connections to LLS. They are Jerry M. Adams, Ph.D, The Walter & Eliza Hall Institute of Medical Research; Jon C Aster, M.D., Ph.D., Brigham and Women's Hospital, Inc.; Carl H. June, M.D., University of Pennsylvania; Jonathan Licht, M.D., Northwestern University.
The innovative SCOR program funds teams of researchers representing different disciplines and engaged in collaborative efforts to discover new approaches to treat patients with hematological malignancies. The teams will each receive $1.25 million a year for five years, for a total of $6.25 million each.
Dr. Adams and his colleagues in The Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia, have been investigating apoptosis, the natural process of cell death, for over two decades. Our bodies make billions of blood cells every day, and, to make room, billions of other blood cells must undergo apoptosis. If some cells fail to die when they should, they can develop into leukemia, lymphoma or multiple myeloma.
The Melbourne team is studying how impaired apoptosis contributes to the development of blood cell cancers and renders the malignant cells more resistant to current therapies. Notably, to improve treatment, they are also studying new drugs, used either alone or in combination with other therapies, which directly engage the apoptotic machinery and flip the cell death switch.
Dr. Aster, Professor of Pathology at Brigham and Women's Hospital, Inc., in Boston,
is working on new therapies for acute lymphoblastic leukemia (ALL) and related blood cancers. One team project is focused on drugs that inhibit bromodomain proteins, a group of proteins shown to maintain the growth and survival of ALL cells and other blood cancer cells.
Another team member is working on drugs that inhibit a protein called DOT1L, shown to have a key role in some forms of acute leukemia that often occur in infants and are frequently fatal with current therapies. Another group is developing new drugs to treat tumors caused by the Notch signaling pathway, which Aster has previously shown is hyperactive in T-cell ALL. In the final project, Adolfo Ferrando, M.D., Ph.D., is identify drugs that overcome resistance to glucocorticoids, a mainstay of current blood cancer therapy that Ferrando has shown stop working when certain other pathways are activated in ALL cells.
"By working as a team, our SCOR aims to move new treatments emanating from each of our projects into the clinic during the next 5 years, thereby providing new hope for patients with blood cancers that are now incurable," Aster said.
Dr. June, a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research at the University of Pennsylvania's Abramson Cancer Center, has demonstrated sustained success employing genetically engineered T cells as a novel targeted therapy for blood cancers.
Over the last ten years, LLS has provided consistent support to Dr. June in the form of SCOR grant funding to support the development of his adoptive immunotherapy programs at Penn. Traditional therapy consisting of allogeneic bone marrow transplantation (using a donor's cells) remains among the most successful treatments for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), but long-term survival of adults is still less than 50 percent.
A key objective of Dr. June's new SCOR project is to achieve or exceed the potent effects observed with traditional stem cell transplantation while eliminating the serious associated risk of graft versus host disease. In addition, standard drug regimens used in leukemia treatment, particularly for AML, are often not curative because they fail to eradicate the leukemia stem cells that are capable of perpetuating the disease after initial treatment has been completed.
The team will perform basic and translational studies to develop new chimeric antigen receptors to kill the stem cells that occur in AML. In studies to be conducted at the University of Pennsylvania and the Children's Hospital of Philadelphia, clinical trials will test new forms of chimeric antigen receptor modified cells in both adult and pediatric blood cancers that are resistant to current therapies. Through multiple collaborations and synergies, these projects have much greater potential to accelerate the development of engineered T cells as novel therapies for ALL and AML.
Dr. Licht, professor and chief, Division of Hematology/Oncology at Northwestern University, along with a distinguished group of co-investigators at Rockefeller University, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center and the University of Michigan studies aberrant epigenetic regulation in leukemia, lymphoma and myeloma. The group studies chromatin, the combination of DNA and protein which contains genes and epigenetics, the chemical and physical changes in chromatin that control how genes are turned on and off.
Recent evidence resulting from the human genome project showed that mutations in proteins that control the chemical structure of chromatin are common in blood cancer. Such mutations have a cascade effect leading to a radical upset of the normal control of genes and uncontrolled cell growth. Many of the proteins that affect chromatin are enzymes and may be targeted for therapy. Dr. Licht's SCOR group includes leukemia biologists, molecular biologists, structural biologists and chemists.
Together they will discover how mutant epigenetic proteins cause blood cancers, develop animal models of these processes, solve the detailed atomic structure of the proteins and begin to develop therapies to reverse the abnormalities. Over the past five years the group published numerous joint papers on the underlying mechanism of leukemia in the highest quality scientific journals. They have analyzed clinical specimens to understand how epigenetic regulation may affect the prognosis of leukemia. Lastly the group in involved in the study of drugs that can reverse abnormal gene regulation in leukemia.
"This year's SCOR teams consist of investigators with illustrious careers, all of whom are undertaking cutting-edge research," said Richard Winneker, Ph.D., LLS senior vice president of research. "Their work is leading to a better understanding of the root causes of blood cancer and the development of new immunotherapies and novel drugs that can target the genetic abnormalities that lead to cancer. LLS is honored to be able to help advance their work and bring more therapies to patients in the near future."
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