DUAL-CONTROLLED DRUG AND PHOTOACTIVATABLE SYSTEM FOR SPATIOTEMPORAL CONTROL OF CELL THERAPY

Provided are compositions, including products of manufacture and kits, and methods, for remotely-controlled and non-invasive manipulation of intracellular nucleic acid expression, genetic processes, function and activity in live cells such as a T cell, a primary T cell, a B cell, a monocyte, a macrophage, a dendritic cell or a natural killercell in vivo, for example, including activating, adding functions or changing or adding specificities for an immune cell, for monitoring physiologic processes, for the correction of pathological processes and for the control of therapeutic outcomes. Provided are tamoxifen-gated photoactivatable split-Cre recombinase optogenetic systems, called TamPA-Cre, that feature high spatiotemporal control to control or alter cell activities in vivo, for example, to limit the activity of a Chimeric Antigen Receptor (CAR)-expressing cell such as an immune cell and its activity at a tumor site for immunotherapy applications.