The project is designed to aid researchers in bringing the basic science of new cellular therapies to human clinical trials, and eventually, to clinical practice--a process known as translational research. The biological therapies represented in the University of Minnesota contract include use of adult stem cells (in particular, multipotent adult progenitor cells, or MAPCs), expansion of umbilical cord blood (UCB) hematopoietic (blood) stem cells, tumor vaccines, and genetically modified immune system cells. In addition, the team will develop a post-doctoral training program in translational medicine and production of somatic cell therapies, in compliance with strict FDA guidelines.
"The potential is great for these therapies," said lead investigator John E. Wagner Jr., M.D., professor of pediatrics and Scientific Director of the Minnesota Molecular and Cellular Therapeutics (MMCT) Facility and of Clinical Research for the Blood and Bone Marrow Transplant Program and of the Stem Cell Institute at the University of Minnesota. "We had the infrastructure to produce the biological materials used in these therapies, and now we have the funding to make them readily available for innovative clinical trials. This funding is an example of how the NIH recognizes the importance of translational research, to help move basic science discoveries more rapidly to direct patient care and treatment."
The University is in the forefront of translational research, as evidenced by the existence of the MMCT facility and the future Translational Research Facility (TRF). Currently, the MMCT, a 36,000 square-foot facility on the St. Paul campus, will house much of the research. The facility provides support for the development of phase I and II clinical trials of advanced cell, tissue, and gene-based therapies by translating research lab technologies into clinically applicable biologic reagents. The programs in the MMCT provide the technical expertise, as well as the regulatory structure, to ensure that all FDA requirements are satisfied.
An example of the ongoing work, Wagner and his team are working on adult stem cells, which may be useful for treating a number of diseases, such as Parkinson's, stroke, diabetes, and heart disease. Researchers at the University of Minnesota Stem Cell Institute (SCI), led by Catherine M. Verfaillie, M.D., have shown that adult bone marrow-derived cells can differentiate into many types of cells, including liver, pancreas, and brain. These multipotent adult progenitor cells (MAPCs) are a major focus of potential stem cell treatments.
Wagner is also investigating the use of umbilical cord blood to treat children and adults with immune disorders, leukemia, tumors, lymphoma, anemias, metabolic disorders, and bone marrow failure. Umbilical cord blood contains stem cells that can be transplanted to produce all blood cells in the human body--red blood cells, white blood cells, and platelets--necessary for creating healthy bone marrow and immune system. "Developing methods to expand the number of stem cells is crucial for the application of umbilical cord blood transplantation in adults," said Wagner.
The team is also working on developing tumor vaccines, a project led by Jeffrey Miller, M.D. Currently, researchers at the University are developing a breast cancer vaccine that is created with a patient's own cancer cells. The vaccine is created by extracting proteins from a patient's breast tumor cells and attaching them to microscopic immunization beads. The vaccine is then injected back into the patient in an effort to trigger the patient's own immune system to destroy cancer cells. This contract with NHLBI will enable further research in tumor vaccines, including prostate, melanoma, and renal cancers.
While immune cells can act as cancer-killing cells, there are risks that these cells could attack the patient's healthy tissue as well. "Genetic modification with a 'suicide' gene provides an added level of safety," stated Wagner. If the cancer-killing cells cause undesirable effects, the cells can be destroyed by activating the 'suicide' gene with an antibiotic. This important research is being led by Paul Orchard, M.D.
"Overall, a key aspect of this multi-million dollar contract is the collaboration it will facilitate," said Wagner. "Instead of competing with each other, we will be pooling our resources and individual areas of expertise to translate cutting-edge basic laboratory studies into care. This will ultimately lead us to breakthrough therapies in the treatment of cancer, heart disease, diabetes, and more."