Grant: Operating Grant

The immune system actively guards against cancer using the 'cytotoxic T lymphocytes', commonly referred to as CTLs. CTLs become activated upon recognition of certain proteins called 'tumor antigens' that are expressed on tumor cells. These tumor-specific CTLs infiltrate the tumor and kill the cancer cells. When the tumor is aggressive and grows into a larger mass, it secretes a variety of substances that neutralize the killing ability of CTLs. These tumor-infiltrating CTLs can be obtained from the tumor, grown in the laboratory outside the suppressive influence of the tumor and injected back into the same patient so that they can now efficiently kill the tumor. This method is called 'adoptive cell therapy' or ACT. ACT is being used in clinical trials to treat melanoma patients. However, the success of this treatment is unpredictable because the biomarkers that define the clinical efficacy of CTLs used for ACT have not yet been adequately defined. In this project, we will use a new strategy developed in our laboratory to optimize the conditions for generating antitumor CTLs with superior antitumor efficacy. Using a mouse model of melanoma, we will determine the parameters that correlate with the clinical efficiacy of antitumor CTLs. We will also investigate the feasibility of generating tumor-specific CTLs from outside the immunosuppressive environment of the tumor, an approach that could pave the way for generating antitumor CTLs from the blood of human cancer patients.