Investigators will develop two imaging tools for assessing the effectiveness of various experimental T cell immunotherapies being developed in mouse models as potential treatments for human brain gliomas.
Given the lack of results and serious side effects from conventional chemotherapies used to try to treat brain glioma, research that is devoted to strengthening the patient’s own immune T cells in the laboratory and then infusing them back into the patient is receiving increasing attention. A major obstacle in developing such “immunotherapies” is the blood-brain-barrier (BBB): Scientists must design effective methods that enable the strengthened immune T cells to migrate from the body, cross the BBB and enter the brain. If that is accomplished, the next challenge is to determine and demonstrate that the immune T cells effectively attack the tumor. The Federal Food and Drug Administration (FDA), which must approve all drugs and biologics for interstate marketing in this country based on evidence of relative safety and efficacy, has expressed an interest in developing methods to non-invasively verify where the immune cells go immediately after being inoculated into the patient, where in the brain the cells have migrated to thereafter, and demonstrate evidence of tumor shrinkage or improved clinical outcome.
Imaging tools recently developed by these investigators, initially to study T cell migration to the pre-diabetic pancreas and now to study their migration to brain glioma, are designed to address these needs. They removed T cells from a mouse model, labeled them in the laboratory with a perfluorocarbon (PFC) emulsion, inoculated the labeled cells back into the mice, and used MRI to track the cells’ migration. They found that this technique provides reliable estimates of the number of cells that reach a specific destination. Moreover, they also discovered that this same PFC emulsion can be used to measure the amount of oxygen present in a cell, and found that increased oxygenation is an early indication of tumor killing. They now hypothesize that this technique can be effectively used in the mouse model of glioma to quantify the number of immune T cells that migrate to the site of brain glioma and that the extent of increase oxygenation (i.e., intracellular partial pressure of oxygen) within glioma cells will correlate with the amount of T cell migration to the tumor. They will test these hypotheses in the mouse glioma model.
Significance: If successful in the mouse model, this new technique then would be tested in patients with glioma to see if it provides valid biomarkers for determining whether specific experimental immunotherapies are effective.