Anti-E5B9 single-chain variable fragment (scFv) domain (Anti-E5B9 scFv)

The Anti-E5B9 single-chain variable fragment (scFv) domain is a specialized antibody-derived component of RevTM (Reversible Transmembrane) adaptor molecules, which are part of the RevCAR modular T-cell therapy platform (Mitwasi et al., 2020). In this "reverse" CAR architecture, T cells are engineered to express a RevCAR that displays a specific peptide epitope, the E5B9 tag, on the cell surface rather than a traditional antigen-binding domain (Kittel-Boselli et al., 2021). The E5B9 tag is derived from the human La/SS-B nuclear protein, making it a highly specific and potentially non-immunogenic target for the adaptor (Arndt et al., 2014). The RevTM adaptor molecule is a bispecific protein consisting of the Anti-E5B9 scFv fused to another scFv targeting a tumor-associated antigen, such as CD123 or PSMA (AvenCell Therapeutics). The Anti-E5B9 scFv domain functions as the bridge-head that anchors the adaptor to the RevCAR T-cell, while the tumor-targeting arm engages the cancer cell, thereby facilitating the formation of an artificial immunological synapse. This modular design allows for the precise control of T-cell activation and intensity through the dosing of the RevTM adaptor, providing a safety switch to mitigate adverse effects like cytokine release syndrome (Mitwasi et al., 2020).

Other names

Anti-La scFv5B9 scFvE5B9-binding domainRevTM binding arm

The Anti-E5B9 scFv domain of the RevTM adaptor molecule mediates the recruitment and activation of RevCAR-engineered T cells by binding specifically to the E5B9 epitope expressed on the T-cell surface (Mitwasi et al., 2020). This interaction, combined with the simultaneous binding of the adaptor's second scFv domain to a tumor-associated antigen, bridges the T cell and the tumor cell to induce targeted cytotoxicity and cytokine release (Kittel-Boselli et al., 2021).