Immune cell therapies represent increasingly powerful treatments for diverse cancers. However, the field is still working to overcome challenges in solid tumors, including poor T cell survival/persistence, inadequate T cell proliferation and cytotoxicity, and an immune suppressive environment within tumors. Many technologies aimed at overcoming these challenges can be toxic and pose substantial safety risks. In this proposal, we will use principles of synthetic biology to create therapeutic T cells with potent anti-tumor activity that is transient in nature with programmed decay rate for improved safety. Using glioblastoma multiforme (GBM) as a test case, we will develop and deploy new gene regulatory circuits (RNA decay circuits) that enable temporal control of enhanced chimeric antigen receptor (CAR) T cell therapies.