The researchers will develop a technique for identifying melanoma cells that have metastasized to the brain and for studying the effects of immunotherapies designed to strengthen immune T cell responses to the melanoma cells.
Melanoma is a highly malignant cancer. Melanoma patients have an impaired blood-brain-barrier that allows the cancer cells to enter the brain and spread. In fact, brain metastases often already exist by the time the diagnosis is made. Finding brain metastases is critical, since most deaths from melanoma are due to brain metastases that resist conventional treatment. While melanoma patients have numerous immune T cells, these cells have been inactivated by the tumors. Receptors for immune T cells are able to differentiate between normal and cancer cells, by recognizing peptides (amino acids) that are bound to proteins on the melanoma cell surface. Since there are many copies of T cell receptors and of proteins on melanoma cell surfaces, however, the immune T receptors bind only weakly to the cancer cells.
The investigators will produce high affinity T cell receptors from T cells isolated from melanoma patients. They will undertake efforts to strengthen the ability of the T cell receptors to bind to the proteins on the melanoma cell surface. The investigators will use various imaging probes, including PET, SPECT and MRI probes, coupled with these strengthened T cell receptors, to identify melanoma cells in the brain. They also will see if the imaging probes enable them to determine how immune cells interact with the tumor in response to immunotherapies designed to strengthen T cell actions.
Significance: The new high affinity T cell receptor probes may provide the ability to visualize melanoma metastases in the brain, to aid in diagnosis, and to assess the effects of immunotherapies in strengthening immune T cell responses against the tumors.