Harnessing T cell metabolism for immunotherapy
Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes is a highly promising approach for the treatment of cancer. A major limitation of ACT is the short half-life of in vitro differentiated effector T cells. Since lymphocyte metabolism is linked to T cell longevity, we hypothesize that altering metabolic programming will impact the longevity and antitumor efficacy of adoptively transferred T cells. To test this, we have miniaturized lymphocyte differentiation conditions and developed protocols to assess how nutrient availability (>800 conditions) affects T cell bioenergetics and longevity. In this proposal we will assess whether conditions that alter T cell bioenergetics and increase T cell longevity also improve antitumor activity in an ACT setting. These results are expected to generate preliminary data to support a grant application investigating how lymphocyte bioenergetics affect the ability of T cells to eradicate cancer.