Dr. Bullock will characterize the nature of melanoma patients’ immune T cell responses to experimental therapeutic cancer vaccines in an effort to improve vaccine efficacy.
Research has demonstrated that a patient’s immune cells often initially recognize a cancer, but that this immune response is short-lived. Based on this principle, therapeutic cancer vaccines are now being designed to stimulate the patients’ own immune T cells to mount a sustained attack against the cancer. While a preventive vaccine acts by introducing a tiny amount of non-harmful, weakened or killed virus to teach immune cells to recognize and attack the virus whenever exposed to it, therapeutic vaccines are being designed to strengthen a cancer patient’s pre-existing immune response to the cancer, and to re-initiate that response at the first sign that the cancer has reappeared and metastasized. Moreover, because therapeutic vaccines stimulate the patient’s immune system to attack only cancer cells, the vaccines’ side effects will be less harmful compared to harsh anti-cancer drugs that kill all rapidly dividing cells, not just the cancer cells.
While about 50 percent of melanoma patients treated with an experimental vaccine develops a sustained response to the vaccine, the other 50 percent develops a transient response characterized by an initial strong reaction that progressively diminishes over the six-week vaccine treatment period. Dr. Bullock hypothesizes that in these patients, the T cells become functionally exhausted, and have a reduced ability to proliferate, attack the cancer, and to differentiate into memory T cells that will recognize the cancer whenever it reappears.
He will test this hypothesis through a series of studies that compare T cell responses in patients who mount sustained responses to melanoma versus those whose responses are transient. He will then identify genes that differentiate the T cell responses of patients in these two groups, and determine whether outcomes (longer time for the cancer to progress, and longer disease-free survival) are better in patients who mount the sustained immune response.