UniCAR peptide epitope on CD123 target module (TM123) (TM123)

The UniCAR peptide epitope on TM123 is a critical component of the modular UniCAR T-cell platform, a switchable immunotherapy system designed to enhance the safety and control of CAR-T cell treatments. In this platform, T-cells are engineered to express a universal chimeric antigen receptor (UniCAR) that targets a specific, non-immunogenic peptide epitope (E5B9) derived from the human nuclear protein La/SS-B, rather than a tumor antigen directly (Loff et al., 2020). TM123 is a bispecific target module (TM) that functions as a bridge, containing the E5B9 epitope and a binding domain specific for CD123 (interleukin-3 receptor alpha chain), which is highly expressed in acute myeloid leukemia (AML) and other hematologic malignancies (Mitwasi et al., 2020). When TM123 is administered, it cross-links UniCAR-T cells to CD123-positive tumor cells, inducing localized T-cell activation and tumor destruction. This modular architecture provides a unique safety mechanism; because the TM has a very short pharmacological half-life of less than 30 minutes, the immune response can be rapidly terminated by halting the TM infusion, thereby mitigating severe adverse events like cytokine release syndrome or off-target effects on healthy hematopoietic progenitor cells (NCT04230265).

Other names

E5B9 epitopeLa epitopeUniCAR-TM-CD123CD123-TMLa/SS-B-derived peptide epitope

The UniCAR-T cell expresses a chimeric antigen receptor specific for the E5B9 peptide epitope. The TM123 target module acts as a bridge, binding to CD123 on tumor cells and presenting the E5B9 epitope to UniCAR-T cells, which triggers T-cell activation and tumor cell lysis (Loff et al., 2020; Mitwasi et al., 2020).