John Ohlfest, Ph.D.

Dr. Ohlfest is an Assistant Professor of Pediatrics in the Division of Hematology, Oncology and Blood and Marrow Transplantation as well as an Assistant Professor of Neurosurgery at the University of Minnesota.

He received his Ph.D. in Genetics, Molecular and Cellular Biology in 2004 and completed his Postdoctoral research with an emphasis on gene therapy in 2005, both at the University of Minnesota in Minneapolis, Minnesota.

Dr. Ohlfest’s research is focused on brain tumor immunology, immunotherapy, and other experimental therapies of brain tumors. The long-term goal of this research is to change the disappointing treatment outcomes by developing safe, less toxic, therapies for treatment of the most malignant forms of brain cancer. We are actively investigating several experimental therapies because it is most likely that a combination of several agents will someday lead to a cure for malignant brain tumors.

• Immunotherapy – vaccines are developed in order to stimulate an anti-tumor immune response that can lead to potent, targeted tumor cell death. These will probably be most effective in the context of residual tumor that remains after surgery. Our work and the work of others has shown that vaccines can lead to the generation of antibody and T cell responses to kill tumor cells. A major benefit to vaccination is that side effects have typically been mild and delivery is simply injection beneath the skin.
• Gene Therapy – tumor cells or normal cells are genetically engineered to secrete proteins that stimulate an anti-tumor immune response, inhibit tumor cell growth directly, or inhibit the growth of blood vessels into the tumor. A major challenge of gene therapy is to develop technologies that “hit” enough of the target cells to have a strong therapeutic effect. Overcoming such delivery obstacles may lead to successful gene therapy for brain tumors in the foreseeable future.
• Drug delivery – both gene therapy and drug therapy suffer from limited delivery of therapeutic agent into the tumor. For gene therapy and direct injection of drugs into the tumor we developed hollow fiber catheters. Hollow fiber catheters can be placed directly into the brain tumor by a neurosurgeon, followed by a slow continuous infusion of therapeutic agent (also known as convection enhanced delivery). For small molecule drugs that are administered intravenously, the blood brain barrier excludes most of the drug from reaching the “migratory” tumor cells that travel away from the main tumor mass. Efflux inhibitors are drugs we are testing that temporarily inhibit the “pumps” in the blood brain barrier responsible for drug efflux.
• Small Molecule Drug Therapy – brain tumors cells often depend on aberrant progrowth signals to continue growing. Such progrowth signals can be provided from a cell surface proteins called a receptor tyrosine kinases that brain tumor cells express at abnormally high levels. A new class of small molecule drugs, known as receptor tyrosine kinase inhibitors (RTKIs) are being developed and tested for treatment of brain cancer. Our focus is to determine the optimal combination of RTKIs to use in combination with other adjuvants therapies to kill brain tumor cells while sparing normal cells.