This laboratory study will examine whether immune system cells of patients with deadly brain tumors, called gliomas, can be enhanced in the laboratory to attack the tumor cells. If so, this could lead to development of a new therapeutic approach to this currently untreatable brain cancer.
Gliomas are particularly virulent brain tumors that are not detected by the patient's immune system. This is because dendritic cells, immune system sentries that ordinarily spot invaders and organize an attack by immune T cells, are not present in the brain. Moreover, only immune T cells that already have been taught to attack a specific antigen (pathogen) are granted entry into the brain by its gatekeeper, the blood-brain-barrier. Further complicating the situation, gloimas are highly heterogeneous. Their many antigens require a coordinated immune response. The Rockefeller researchers hypothesize, however, that dendritic cells can be experimentally induced to activate a coordinated attack by the body's two types of immune cells: innate immune cells (which usually mount a short, generalized attack) and adaptive immune cells (which mount a highly directed and sustained attack against a specific invader).
This hypothesis is based on the researchers' recent finding that certain innate immune cells, called "Natural Killer" (NK) T cells, are present and functioning in the blood of glioma patients. In laboratory studies, these innate NKT cells can destroy certain glioma molecules that are present both in the tumors and in the blood vessels that supply them. Now the investigators want to determine whether they can modify dendritic cells in the laboratory to stimulate both the innate NKT cells and the adaptive immune system's T cells to attack these glioma molecules.
First, the investigators will obtain blood samples from glioma patients and determine whether their NKT cells are able to be expanded in the laboratory to respond to this specific glioma molecule. Then the investigators will conduct laboratory studies to determine how best to acquaint dendritic cells with glioma antigens, so that the dendritic cells can instruct immune T cells to recognize and attack the antigens. Finally, the researchers will undertake preliminary laboratory experiments to test whether the combined presence of innate NKT cells and instructed T cells leads to enhanced killing of tumor cells. If so, this will pave the way for future efforts to see if patients' immune cells, once enhanced in the laboratory, can be re-introduced into their bodies to mount a strong, coordinated attack against glioma.