Adoptive transfer of T cells expressing a chimeric antigen receptor (CAR) has yielded impressive results in patients with select hematologic malignancies. However, CAR T cell therapy has been less effective in solid tumors with heterogeneous antigen expression and the inability to regulate the activity of CAR T cells after infusion is a significant safety concern. To address these issues, we developed highly adaptable CAR T cell systems that consist of tagged bi-functional targeting ligands that selectively and exclusively bind to universal immune receptors expressed by engineered T lymphocytes, and the desired antigen, thus selectively redirecting CAR T cell activity via a bi-functional protein bridge. Unlike conventional CAR T cells, this platform enables precision control over engineered CAR T cell function and specificity through antibody dosing to deliver the desired antitumor activity and improve safety. Further, the adaptable specificity enables either simultaneous or sequential multi-antigen attack to address tumor antigen heterogeneity and antigen loss/escape. Since our original discovery, a variety of universal immune receptors have been developed and tested, and clinical trials initiated. While the promise of these approaches remains significant, the impacts of architecture, geometry, valency, orientation and avidity are being investigated. Our most recent data suggests, that incorporation of covalent binding partners into universal immune receptor systems can stabilize CAR formation, redirect antigen specificity on demand, and permit studies of receptor turnover. We anticipate that the dose dependent control of CAR T cell activity provided by universal immune receptor systems will aid in preventing cytokine release syndrome in patients receiving CAR T cell infusion, address issues of tumor antigen heterogeneity/loss, and permit better control over CAR T cell activation and persistence after administration.