Synthetic UniCAR peptide epitope (UniCAR epitope)

The Synthetic UniCAR peptide epitope is a critical component of the modular Universal Chimeric Antigen Receptor (UniCAR) T-cell system, designed to enhance the safety and flexibility of CAR-T therapies. Unlike conventional CAR-T cells that directly bind to tumor antigens, UniCAR-T cells are engineered to recognize a specific, non-immunogenic synthetic peptide (often the E5B9 epitope derived from the human nuclear protein La/SS-B) that is otherwise absent from the cell surface. This epitope is integrated into soluble adapter molecules called Targeting Modules (TMs), which possess dual specificity for both the UniCAR-T cell and a chosen tumor-associated antigen. By administering these TMs, clinicians can cross-link UniCAR-T cells to tumor cells, effectively turning the T-cell activity 'on' or 'off' based on the presence and half-life of the TM. This system allows for the targeting of multiple different antigens using a single T-cell product and provides a mechanism to mitigate severe adverse effects like cytokine release syndrome by ceasing TM administration. Clinical applications of this technology, such as UniCAR02-T cells combined with CD123-specific TMs, are currently being investigated for the treatment of relapsed or refractory acute myeloid leukemia.

Other names

E5B9 peptide epitopeLa-derived epitopeUniCAR tagSynthetic E5B9 peptide

The synthetic UniCAR peptide epitope serves as a bridge between a modular Chimeric Antigen Receptor (CAR) T-cell and a tumor cell. The UniCAR-T cell is engineered to express a receptor specific for this synthetic peptide, which is not naturally found on the cell surface. A bispecific Targeting Module (TM) is administered, which contains the UniCAR epitope and a binding domain for a tumor-associated antigen. When the TM binds to the tumor cell, the UniCAR-T cell recognizes the presented epitope, leading to the formation of an immunological synapse, T-cell activation, and targeted lysis of the cancer cell.