E5B9 peptide epitope – Reversible T-cell Modulator (RevTM) adaptor interface (E5B9-RevTM interface)

The E5B9 peptide epitope – RevTM adaptor interface is the central structural and functional component of the Reversible T-cell Modulator (RevTM) switchable CAR-T platform developed by Calibr at Scripps Research (Kim et al., 2015). This system utilizes a universal CAR-T cell, such as CLBR001, which is engineered to recognize a specific synthetic peptide tag known as the E5B9 epitope, rather than a tumor antigen directly (ClinicalTrials.gov, NCT04450069). The E5B9 epitope, a 10-amino acid sequence derived from the human nuclear protein La/SS-B, is incorporated into a bispecific RevTM adaptor molecule that also contains a targeting domain for a specific cancer antigen like CD19 or HER2 (Viaud et al., 2018). When the RevTM adaptor is administered, it creates a bridge between the sCAR-T cell and the tumor cell, forming a synthetic immunological synapse that triggers T-cell activation and tumor lysis. This modular design allows for precise control over the intensity of the immune response by adjusting the dosage of the adaptor, providing a safety mechanism to mitigate toxicities like cytokine release syndrome. Furthermore, the platform enables the targeting of multiple different antigens using the same universal CAR-T cell product simply by switching or combining different RevTM adaptors (Scripps Research, 2020).

Other names

E5B9 tagE5B9-CAR interfaceSwitchable CAR-T adaptor interfacesCAR-T switch interfaceE5B9 peptide-scFv complex

The E5B9-RevTM interface functions as a synthetic molecular bridge where the E5B9 peptide epitope on a bispecific adaptor molecule is recognized by a universal chimeric antigen receptor (CAR) expressed on T-cells, while the other end of the adaptor binds to a tumor-associated antigen, thereby facilitating T-cell activation and tumor cell lysis only in the presence of the adaptor.